---
_id: '6995'
abstract:
- lang: eng
text: Human brain organoids represent a powerful tool for the study of human neurological
diseases particularly those that impact brain growth and structure. However, many
neurological diseases lack obvious anatomical abnormalities, yet significantly
impact neural network functions, raising the question of whether organoids possess
sufficient neural network architecture and complexity to model these conditions.
Here, we explore the network level functions of brain organoids using calcium
sensor imaging and extracellular recording approaches that together reveal the
existence of complex oscillatory network behaviors reminiscent of intact brain
preparations. We further demonstrate strikingly abnormal epileptiform network
activity in organoids derived from a Rett Syndrome patient despite only modest
anatomical differences from isogenically matched controls, and rescue with an
unconventional neuromodulatory drug Pifithrin-α. Together, these findings provide
an essential foundation for the utilization of human brain organoids to study
intact and disordered human brain network formation and illustrate their utility
in therapeutic discovery.
acknowledgement: We thank S. Butler, T. Carmichael and members of the laboratory of
B.G.N. for helpful discussions and comments on the manuscript; N. Vishlaghi and
F. Turcios-Hernandez for technical assistance, and J. Lee, S.-K. Lee, H. Shinagawa
and K. Yoshikawa for valuable reagents. We also thank the UCLA Eli and Edythe Broad
Stem Cell Research Center (BSCRC) and Intellectual and Developmental Disabilities
Research Center microscopy cores for access to imaging facilities. This work was
supported by grants from the California Institute for Regenerative Medicine (CIRM)
(DISC1-08819 to B.G.N.), the National Institute of Health (R01NS089817, R01DA051897
and P50HD103557 to B.G.N.; K08NS119747 to R.A.S.; K99HD096105 to M.W.; R01MH123922,
R01MH121521 and P50HD103557 to M.J.G.; R01GM099134 to K.P.; R01NS103788 to W.E.L.;
R01NS088571 to J.M.P.; R01NS030549 and R01AG050474 to I.M.), and research awards
from the UCLA Jonsson Comprehensive Cancer Center and BSCRC Ablon Scholars Program
(to B.G.N.), the BSCRC Innovation Program (to B.G.N., K.P. and W.E.L.), the UCLA
BSCRC Steffy Brain Aging Research Fund (to B.G.N. and W.E.L.) and the UCLA Clinical
and Translational Science Institute (to B.G.N.), Paul Allen Family Foundation Frontiers
Group (to K.P. and W.E.L.), the March of Dimes Foundation (to W.E.L.) and the Simons
Foundation Autism Research Initiative Bridge to Independence Program (to R.A.S.
and M.J.G.). R.A.S. was also supported by the UCLA/NINDS Translational Neuroscience
Training Grant (R25NS065723), a Research and Training Fellowship from the American
Epilepsy Society, a Taking Flight Award from CURE Epilepsy and a Clinician Scientist
training award from the UCLA BSCRC. J.E.B. was supported by the UCLA BSCRC Rose
Hills Foundation Graduate Scholarship Training Program. M.W. was supported by postdoctoral
training awards provided by the UCLA BSCRC and the Uehara Memorial Foundation. O.A.M.
and A.K. were supported in part by the UCLA-California State University Northridge
CIRM-Bridges training program (EDUC2-08411). We also acknowledge the support of
the IDDRC Cells, Circuits and Systems Analysis, Microscopy and Genetics and Genomics
Cores of the Semel Institute of Neuroscience at UCLA, which are supported by the
NICHD (U54HD087101 and P50HD10355701). We lastly acknowledge support from a Quantitative
and Computational Biosciences Collaboratory Postdoctoral Fellowship to S.M. and
the Quantitative and Computational Biosciences Collaboratory community, directed
by M. Pellegrini.
alternative_title:
- Nature Neuroscience
article_processing_charge: Yes
author:
- first_name: Ranmal A.
full_name: Samarasinghe, Ranmal A.
last_name: Samarasinghe
- first_name: Osvaldo
full_name: Miranda, Osvaldo
id: 862A3C56-A8BF-11E9-B4FA-D9E3E5697425
last_name: Miranda
orcid: 0000-0001-6618-6889
- first_name: Jessie E.
full_name: Buth, Jessie E.
last_name: Buth
- first_name: Simon
full_name: Mitchell, Simon
last_name: Mitchell
- first_name: Isabella
full_name: Ferando, Isabella
last_name: Ferando
- first_name: Momoko
full_name: Watanabe, Momoko
last_name: Watanabe
- first_name: Arinnae
full_name: Kurdian, Arinnae
last_name: Kurdian
- first_name: Peyman
full_name: Golshani, Peyman
last_name: Golshani
- first_name: Kathrin
full_name: Plath, Kathrin
last_name: Plath
- first_name: William E.
full_name: Lowry, William E.
last_name: Lowry
- first_name: Jack M.
full_name: Parent, Jack M.
last_name: Parent
- first_name: Istvan
full_name: Mody, Istvan
last_name: Mody
- first_name: Bennett G.
full_name: Novitch, Bennett G.
last_name: Novitch
citation:
ama: Samarasinghe RA, Miranda O, Buth JE, et al. Identification of Neural Oscillations
and Epileptiform Changes in Human Brain Organoids. Vol 24. Springer Nature;
2021. doi:10.1038/s41593-021-00906-5
apa: Samarasinghe, R. A., Miranda, O., Buth, J. E., Mitchell, S., Ferando, I., Watanabe,
M., … Novitch, B. G. (2021). Identification of neural oscillations and epileptiform
changes in human brain organoids (Vol. 24). Springer Nature. https://doi.org/10.1038/s41593-021-00906-5
chicago: Samarasinghe, Ranmal A., Osvaldo Miranda, Jessie E. Buth, Simon Mitchell,
Isabella Ferando, Momoko Watanabe, Arinnae Kurdian, et al. Identification of
Neural Oscillations and Epileptiform Changes in Human Brain Organoids. Vol.
24. Springer Nature, 2021. https://doi.org/10.1038/s41593-021-00906-5.
ieee: R. A. Samarasinghe et al., Identification of neural oscillations
and epileptiform changes in human brain organoids, vol. 24. Springer Nature,
2021.
ista: Samarasinghe RA, Miranda O, Buth JE, Mitchell S, Ferando I, Watanabe M, Kurdian
A, Golshani P, Plath K, Lowry WE, Parent JM, Mody I, Novitch BG. 2021. Identification
of neural oscillations and epileptiform changes in human brain organoids, Springer
Nature, 32p.
mla: Samarasinghe, Ranmal A., et al. Identification of Neural Oscillations and
Epileptiform Changes in Human Brain Organoids. Vol. 24, Springer Nature, 2021,
doi:10.1038/s41593-021-00906-5.
short: R.A. Samarasinghe, O. Miranda, J.E. Buth, S. Mitchell, I. Ferando, M. Watanabe,
A. Kurdian, P. Golshani, K. Plath, W.E. Lowry, J.M. Parent, I. Mody, B.G. Novitch,
Identification of Neural Oscillations and Epileptiform Changes in Human Brain
Organoids, Springer Nature, 2021.
date_created: 2019-11-10T11:23:58Z
date_published: 2021-08-23T00:00:00Z
date_updated: 2023-08-04T10:49:44Z
day: '23'
department:
- _id: GradSch
- _id: SiHi
doi: 10.1038/s41593-021-00906-5
external_id:
isi:
- '000687516300001'
pmid:
- '34426698 '
intvolume: ' 24'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1038/s41593-021-00906-5
month: '08'
oa: 1
oa_version: Published Version
page: '32'
pmid: 1
publication_identifier:
eissn:
- 1546-1726
issn:
- 1097-6256
publication_status: published
publisher: Springer Nature
status: public
title: Identification of neural oscillations and epileptiform changes in human brain
organoids
type: technical_report
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 24
year: '2021'
...
---
_id: '8546'
abstract:
- lang: eng
text: Brain neurons arise from relatively few progenitors generating an enormous
diversity of neuronal types. Nonetheless, a cardinal feature of mammalian brain
neurogenesis is thought to be that excitatory and inhibitory neurons derive from
separate, spatially segregated progenitors. Whether bi-potential progenitors with
an intrinsic capacity to generate both lineages exist and how such a fate decision
may be regulated are unknown. Using cerebellar development as a model, we discover
that individual progenitors can give rise to both inhibitory and excitatory lineages.
Gradations of Notch activity determine the fates of the progenitors and their
daughters. Daughters with the highest levels of Notch activity retain the progenitor
fate, while intermediate levels of Notch activity generate inhibitory neurons,
and daughters with very low levels of Notch signaling adopt the excitatory fate.
Therefore, Notch-mediated binary cell fate choice is a mechanism for regulating
the ratio of excitatory to inhibitory neurons from common progenitors.
acknowledgement: This work was supported by the program “Investissements d’avenir”
ANR-10-IAIHU-06 , ICM , a Sorbonne Université Emergence grant, an Allen Distinguished
Investigator Award , and the Roger De Spoelberch Foundation Prize (to B.A.H.); Armenise-Harvard
Foundation , AIRC , and CARITRO (to L.T.); and the European Research Council under
the European Union’s Horizon 2020 research and innovation programme grant agreement
no. 725780 LinPro (to S.H.). T.Z. and T.L. were supported by doctoral fellowships
from the China Scholarship Council and A.H.H. by a doctoral DOC fellowship of the
Austrian Academy of Sciences ( 24812 ). All animal work was conducted at the PHENO-ICMice
facility. The Core is supported by 2 “Investissements d’avenir” (ANR-10- IAIHU-06
and ANR-11-INBS-0011-NeurATRIS) and the “Fondation pour la Recherche Médicale.”
Light microscopy work was carried out at ICM’s imaging core facility, ICM.Quant,
and analysis of scRNA-seq data was carried out at ICM’s bioinformatics core facility,
iCONICS. We thank Paulina Ejsmont, Natalia Danda, and Nathalie De Geest for technical
support. We are grateful to Dr. Shahragim TAJBAKHSH for providing R26Rstop-NICD-nGFP
transgenic mice, Dr. Bart De Strooper for Psn1-deficient mice, Dr. Jean-Christophe
Marine for Gt(ROSA)26SortdTom reporter mice, and Dr. Martinez Barbera for Sox2CreERT2
mice. We also give thanks to Dr. Mikio Hoshino for providing Atoh1 and Ptf1a antibodies.
B.A.H. is an Einstein Visiting Fellow of the Berlin Institute of Health .
article_number: '109208'
article_processing_charge: No
article_type: original
author:
- first_name: Tingting
full_name: Zhang, Tingting
last_name: Zhang
- first_name: Tengyuan
full_name: Liu, Tengyuan
last_name: Liu
- first_name: Natalia
full_name: Mora, Natalia
last_name: Mora
- first_name: Justine
full_name: Guegan, Justine
last_name: Guegan
- first_name: Mathilde
full_name: Bertrand, Mathilde
last_name: Bertrand
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Marica
full_name: Anderle, Marica
last_name: Anderle
- first_name: Natasha
full_name: Danda, Natasha
last_name: Danda
- first_name: Luca
full_name: Tiberi, Luca
last_name: Tiberi
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Bassem A.
full_name: Hassan, Bassem A.
last_name: Hassan
citation:
ama: Zhang T, Liu T, Mora N, et al. Generation of excitatory and inhibitory neurons
from common progenitors via Notch signaling in the cerebellum. Cell Reports.
2021;35(10). doi:10.1016/j.celrep.2021.109208
apa: Zhang, T., Liu, T., Mora, N., Guegan, J., Bertrand, M., Contreras, X., … Hassan,
B. A. (2021). Generation of excitatory and inhibitory neurons from common progenitors
via Notch signaling in the cerebellum. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2021.109208
chicago: Zhang, Tingting, Tengyuan Liu, Natalia Mora, Justine Guegan, Mathilde Bertrand,
Ximena Contreras, Andi H Hansen, et al. “Generation of Excitatory and Inhibitory
Neurons from Common Progenitors via Notch Signaling in the Cerebellum.” Cell
Reports. Elsevier, 2021. https://doi.org/10.1016/j.celrep.2021.109208.
ieee: T. Zhang et al., “Generation of excitatory and inhibitory neurons from
common progenitors via Notch signaling in the cerebellum,” Cell Reports,
vol. 35, no. 10. Elsevier, 2021.
ista: Zhang T, Liu T, Mora N, Guegan J, Bertrand M, Contreras X, Hansen AH, Streicher
C, Anderle M, Danda N, Tiberi L, Hippenmeyer S, Hassan BA. 2021. Generation of
excitatory and inhibitory neurons from common progenitors via Notch signaling
in the cerebellum. Cell Reports. 35(10), 109208.
mla: Zhang, Tingting, et al. “Generation of Excitatory and Inhibitory Neurons from
Common Progenitors via Notch Signaling in the Cerebellum.” Cell Reports,
vol. 35, no. 10, 109208, Elsevier, 2021, doi:10.1016/j.celrep.2021.109208.
short: T. Zhang, T. Liu, N. Mora, J. Guegan, M. Bertrand, X. Contreras, A.H. Hansen,
C. Streicher, M. Anderle, N. Danda, L. Tiberi, S. Hippenmeyer, B.A. Hassan, Cell
Reports 35 (2021).
date_created: 2020-09-21T12:00:48Z
date_published: 2021-06-08T00:00:00Z
date_updated: 2023-08-04T11:00:48Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.celrep.2021.109208
ec_funded: 1
external_id:
isi:
- '000659894300001'
pmid:
- '34107249 '
file:
- access_level: open_access
checksum: 7def3d42ebc8f5675efb6f38819e3e2e
content_type: application/pdf
creator: cziletti
date_created: 2021-06-15T14:01:35Z
date_updated: 2021-06-15T14:01:35Z
file_id: '9554'
file_name: 2021_CellReports_Zhang.pdf
file_size: 8900385
relation: main_file
success: 1
file_date_updated: 2021-06-15T14:01:35Z
has_accepted_license: '1'
intvolume: ' 35'
isi: 1
issue: '10'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular Mechanisms of Radial Neuronal Migration
publication: Cell Reports
publication_identifier:
eissn:
- ' 22111247'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- relation: earlier_version
url: https://doi.org/10.1101/2020.03.18.997205
scopus_import: '1'
status: public
title: Generation of excitatory and inhibitory neurons from common progenitors via
Notch signaling in the cerebellum
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 35
year: '2021'
...
---
_id: '9188'
abstract:
- lang: eng
text: Genomic imprinting is an epigenetic mechanism that results in parental allele-specific
expression of ~1% of all genes in mouse and human. Imprinted genes are key developmental
regulators and play pivotal roles in many biological processes such as nutrient
transfer from the mother to offspring and neuronal development. Imprinted genes
are also involved in human disease, including neurodevelopmental disorders, and
often occur in clusters that are regulated by a common imprint control region
(ICR). In extra-embryonic tissues ICRs can act over large distances, with the
largest surrounding Igf2r spanning over 10 million base-pairs. Besides classical
imprinted expression that shows near exclusive maternal or paternal expression,
widespread biased imprinted expression has been identified mainly in brain. In
this review we discuss recent developments mapping cell type specific imprinted
expression in extra-embryonic tissues and neocortex in the mouse. We highlight
the advantages of using an inducible uniparental chromosome disomy (UPD) system
to generate cells carrying either two maternal or two paternal copies of a specific
chromosome to analyze the functional consequences of genomic imprinting. Mosaic
Analysis with Double Markers (MADM) allows fluorescent labeling and concomitant
induction of UPD sparsely in specific cell types, and thus to over-express or
suppress all imprinted genes on that chromosome. To illustrate the utility of
this technique, we explain how MADM-induced UPD revealed new insights about the
function of the well-studied Cdkn1c imprinted gene, and how MADM-induced UPDs
led to identification of highly cell type specific phenotypes related to perturbed
imprinted expression in the mouse neocortex. Finally, we give an outlook on how
MADM could be used to probe cell type specific imprinted expression in other tissues
in mouse, particularly in extra-embryonic tissues.
acknowledgement: We thank Melissa Stouffer for critically reading the manuscript.
This work was supported by IST Austria institutional funds; NÖ Forschung und Bildung
n[f + b] life science call grant (C13-002) to S.H. and the European Research Council
(ERC) under the European Union's Horizon 2020 research and innovation program (grant
agreement 725780 LinPro) to S.H.
article_number: '104986'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
- first_name: Quanah
full_name: Hudson, Quanah
last_name: Hudson
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Pauler F, Hudson Q, Laukoter S, Hippenmeyer S. Inducible uniparental chromosome
disomy to probe genomic imprinting at single-cell level in brain and beyond. Neurochemistry
International. 2021;145(5). doi:10.1016/j.neuint.2021.104986
apa: Pauler, F., Hudson, Q., Laukoter, S., & Hippenmeyer, S. (2021). Inducible
uniparental chromosome disomy to probe genomic imprinting at single-cell level
in brain and beyond. Neurochemistry International. Elsevier. https://doi.org/10.1016/j.neuint.2021.104986
chicago: Pauler, Florian, Quanah Hudson, Susanne Laukoter, and Simon Hippenmeyer.
“Inducible Uniparental Chromosome Disomy to Probe Genomic Imprinting at Single-Cell
Level in Brain and Beyond.” Neurochemistry International. Elsevier, 2021.
https://doi.org/10.1016/j.neuint.2021.104986.
ieee: F. Pauler, Q. Hudson, S. Laukoter, and S. Hippenmeyer, “Inducible uniparental
chromosome disomy to probe genomic imprinting at single-cell level in brain and
beyond,” Neurochemistry International, vol. 145, no. 5. Elsevier, 2021.
ista: Pauler F, Hudson Q, Laukoter S, Hippenmeyer S. 2021. Inducible uniparental
chromosome disomy to probe genomic imprinting at single-cell level in brain and
beyond. Neurochemistry International. 145(5), 104986.
mla: Pauler, Florian, et al. “Inducible Uniparental Chromosome Disomy to Probe Genomic
Imprinting at Single-Cell Level in Brain and Beyond.” Neurochemistry International,
vol. 145, no. 5, 104986, Elsevier, 2021, doi:10.1016/j.neuint.2021.104986.
short: F. Pauler, Q. Hudson, S. Laukoter, S. Hippenmeyer, Neurochemistry International
145 (2021).
date_created: 2021-02-23T12:31:43Z
date_published: 2021-05-01T00:00:00Z
date_updated: 2023-08-07T13:48:26Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.neuint.2021.104986
ec_funded: 1
external_id:
isi:
- '000635575000005'
pmid:
- '33600873'
file:
- access_level: open_access
checksum: c6d7a40089cd29e289f9b22e75768304
content_type: application/pdf
creator: kschuh
date_created: 2021-08-11T12:30:38Z
date_updated: 2021-08-11T12:30:38Z
file_id: '9883'
file_name: 2021_NCI_Pauler.pdf
file_size: 7083499
relation: main_file
success: 1
file_date_updated: 2021-08-11T12:30:38Z
has_accepted_license: '1'
intvolume: ' 145'
isi: 1
issue: '5'
keyword:
- Cell Biology
- Cellular and Molecular Neuroscience
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 25D92700-B435-11E9-9278-68D0E5697425
grant_number: LS13-002
name: Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain
publication: Neurochemistry International
publication_identifier:
issn:
- 0197-0186
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell
level in brain and beyond
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 145
year: '2021'
...
---
_id: '9601'
abstract:
- lang: eng
text: 'In mammalian genomes, differentially methylated regions (DMRs) and histone
marks including trimethylation of histone 3 lysine 27 (H3K27me3) at imprinted
genes are asymmetrically inherited to control parentally-biased gene expression.
However, neither parent-of-origin-specific transcription nor imprints have been
comprehensively mapped at the blastocyst stage of preimplantation development.
Here, we address this by integrating transcriptomic and epigenomic approaches
in mouse preimplantation embryos. We find that seventy-one genes exhibit previously
unreported parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted
expressed). Uniparental expression of nBiX genes disappears soon after implantation.
Micro-whole-genome bisulfite sequencing (µWGBS) of individual uniparental blastocysts
detects 859 DMRs. We further find that 16% of nBiX genes are associated with a
DMR, whereas most are associated with parentally-biased H3K27me3, suggesting a
role for Polycomb-mediated imprinting in blastocysts. nBiX genes are clustered:
five clusters contained at least one published imprinted gene, and five clusters
exclusively contained nBiX genes. These data suggest that early development undergoes
a complex program of stage-specific imprinting involving different tiers of regulation.'
acknowledgement: The authors thank Robert Feil and Anton Wutz for helpful discussions
and comments, Samuel Collombet and Peter Fraser for sharing embryo TAD coordinates,
and Andy Riddel at the Cambridge Stem Cell Institute and Thomas Sauer at the Max
Perutz Laboratories FACS facility for flow-sorting. We thank the team of the Biomedical
Sequencing Facility at the CeMM and the Vienna Biocenter Core Facilities (VBCF)
for support with next-generation sequencing. We are grateful to animal care teams
at the University of Bath and MRC Harwell. A.C.F.P. acknowledges support from the
UK Medical Research Council (MR/N000080/1 and MR/N020294/1) and Biotechnology and
Biological Sciences Research Council (BB/P009506/1). L.S. is part of the FWF doctoral
programme SMICH and supported by an Austrian Academy of Sciences DOC Fellowship.
M.L. is funded by a Vienna Research Group for Young Investigators grant (VRG14-006)
by the Vienna Science and Technology Fund (WWTF) and by the Austrian Science Fund
FWF (I3786 and P31334).
article_number: '3804'
article_processing_charge: No
article_type: original
author:
- first_name: Laura
full_name: Santini, Laura
last_name: Santini
- first_name: Florian
full_name: Halbritter, Florian
last_name: Halbritter
- first_name: Fabian
full_name: Titz-Teixeira, Fabian
last_name: Titz-Teixeira
- first_name: Toru
full_name: Suzuki, Toru
last_name: Suzuki
- first_name: Maki
full_name: Asami, Maki
last_name: Asami
- first_name: Xiaoyan
full_name: Ma, Xiaoyan
last_name: Ma
- first_name: Julia
full_name: Ramesmayer, Julia
last_name: Ramesmayer
- first_name: Andreas
full_name: Lackner, Andreas
last_name: Lackner
- first_name: Nick
full_name: Warr, Nick
last_name: Warr
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Ernest
full_name: Laue, Ernest
last_name: Laue
- first_name: Matthias
full_name: Farlik, Matthias
last_name: Farlik
- first_name: Christoph
full_name: Bock, Christoph
last_name: Bock
- first_name: Andreas
full_name: Beyer, Andreas
last_name: Beyer
- first_name: Anthony C.F.
full_name: Perry, Anthony C.F.
last_name: Perry
- first_name: Martin
full_name: Leeb, Martin
last_name: Leeb
citation:
ama: Santini L, Halbritter F, Titz-Teixeira F, et al. Genomic imprinting in mouse
blastocysts is predominantly associated with H3K27me3. Nature Communications.
2021;12(1). doi:10.1038/s41467-021-23510-4
apa: Santini, L., Halbritter, F., Titz-Teixeira, F., Suzuki, T., Asami, M., Ma,
X., … Leeb, M. (2021). Genomic imprinting in mouse blastocysts is predominantly
associated with H3K27me3. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-021-23510-4
chicago: Santini, Laura, Florian Halbritter, Fabian Titz-Teixeira, Toru Suzuki,
Maki Asami, Xiaoyan Ma, Julia Ramesmayer, et al. “Genomic Imprinting in Mouse
Blastocysts Is Predominantly Associated with H3K27me3.” Nature Communications.
Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23510-4.
ieee: L. Santini et al., “Genomic imprinting in mouse blastocysts is predominantly
associated with H3K27me3,” Nature Communications, vol. 12, no. 1. Springer
Nature, 2021.
ista: Santini L, Halbritter F, Titz-Teixeira F, Suzuki T, Asami M, Ma X, Ramesmayer
J, Lackner A, Warr N, Pauler F, Hippenmeyer S, Laue E, Farlik M, Bock C, Beyer
A, Perry ACF, Leeb M. 2021. Genomic imprinting in mouse blastocysts is predominantly
associated with H3K27me3. Nature Communications. 12(1), 3804.
mla: Santini, Laura, et al. “Genomic Imprinting in Mouse Blastocysts Is Predominantly
Associated with H3K27me3.” Nature Communications, vol. 12, no. 1, 3804,
Springer Nature, 2021, doi:10.1038/s41467-021-23510-4.
short: L. Santini, F. Halbritter, F. Titz-Teixeira, T. Suzuki, M. Asami, X. Ma,
J. Ramesmayer, A. Lackner, N. Warr, F. Pauler, S. Hippenmeyer, E. Laue, M. Farlik,
C. Bock, A. Beyer, A.C.F. Perry, M. Leeb, Nature Communications 12 (2021).
date_created: 2021-06-27T22:01:46Z
date_published: 2021-07-12T00:00:00Z
date_updated: 2023-08-10T13:53:23Z
day: '12'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1038/s41467-021-23510-4
external_id:
isi:
- '000667248600005'
file:
- access_level: open_access
checksum: 75dd89d09945185b2d14b2434a0bcb50
content_type: application/pdf
creator: asandaue
date_created: 2021-06-28T08:04:22Z
date_updated: 2021-06-28T08:04:22Z
file_id: '9608'
file_name: 2021_NatureCommunications_Santini.pdf
file_size: 2156554
relation: main_file
success: 1
file_date_updated: 2021-06-28T08:04:22Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
issue: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
publication: Nature Communications
publication_identifier:
eissn:
- '20411723'
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2021'
...
---
_id: '9603'
abstract:
- lang: eng
text: Mosaic analysis with double markers (MADM) offers one approach to visualize
and concomitantly manipulate genetically defined cells in mice with single-cell
resolution. MADM applications include the analysis of lineage, single-cell morphology
and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous
gene functions in vivo in health and disease. Yet, MADM can only be applied to
<25% of all mouse genes on select chromosomes to date. To overcome this limitation,
we generate transgenic mice with knocked-in MADM cassettes near the centromeres
of all 19 autosomes and validate their use across organs. With this resource,
>96% of the entire mouse genome can now be subjected to single-cell genetic mosaic
analysis. Beyond a proof of principle, we apply our MADM library to systematically
trace sister chromatid segregation in distinct mitotic cell lineages. We find
striking chromosome-specific biases in segregation patterns, reflecting a putative
mechanism for the asymmetric segregation of genetic determinants in somatic stem
cell division.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: We thank the Bioimaging, Life Science, and Pre-Clinical Facilities
at IST Austria; M.P. Postiglione, C. Simbriger, K. Valoskova, C. Schwayer, T. Hussain,
M. Pieber, and V. Wimmer for initial experiments, technical support, and/or assistance;
R. Shigemoto for sharing iv (Dnah11 mutant) mice; and M. Sixt and all members of
the Hippenmeyer lab for discussion. This work was supported by National Institutes
of Health grants ( R01-NS050580 to L.L. and F32MH096361 to L.A.S.). L.L. is an investigator
of HHMI. N.A. received support from FWF Firnberg-Programm ( T 1031 ). A.H.H. is
a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences . This
work also received support from IST Austria institutional funds , FWF SFB F78 to
S.H., the People Programme (Marie Curie Actions) of the European Union’s Seventh
Framework Programme ( FP7/2007-2013 ) under REA grant agreement no 618444 to S.H.,
and the European Research Council (ERC) under the European Union’s Horizon 2020
Research and Innovation Programme (grant agreement no. 725780 LinPro ) to S.H.
article_number: '109274'
article_processing_charge: No
article_type: original
author:
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Amarbayasgalan
full_name: Davaatseren, Amarbayasgalan
id: 70ADC922-B424-11E9-99E3-BA18E6697425
last_name: Davaatseren
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Johanna
full_name: Sonntag, Johanna
id: 32FE7D7C-F248-11E8-B48F-1D18A9856A87
last_name: Sonntag
- first_name: Lill
full_name: Andersen, Lill
last_name: Andersen
- first_name: Tina
full_name: Bernthaler, Tina
last_name: Bernthaler
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Anna-Magdalena
full_name: Heger, Anna-Magdalena
id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87
last_name: Heger
- first_name: Randy L.
full_name: Johnson, Randy L.
last_name: Johnson
- first_name: Lindsay A.
full_name: Schwarz, Lindsay A.
last_name: Schwarz
- first_name: Liqun
full_name: Luo, Liqun
last_name: Luo
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Contreras X, Amberg N, Davaatseren A, et al. A genome-wide library of MADM
mice for single-cell genetic mosaic analysis. Cell Reports. 2021;35(12).
doi:10.1016/j.celrep.2021.109274
apa: Contreras, X., Amberg, N., Davaatseren, A., Hansen, A. H., Sonntag, J., Andersen,
L., … Hippenmeyer, S. (2021). A genome-wide library of MADM mice for single-cell
genetic mosaic analysis. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2021.109274
chicago: Contreras, Ximena, Nicole Amberg, Amarbayasgalan Davaatseren, Andi H Hansen,
Johanna Sonntag, Lill Andersen, Tina Bernthaler, et al. “A Genome-Wide Library
of MADM Mice for Single-Cell Genetic Mosaic Analysis.” Cell Reports. Cell
Press, 2021. https://doi.org/10.1016/j.celrep.2021.109274.
ieee: X. Contreras et al., “A genome-wide library of MADM mice for single-cell
genetic mosaic analysis,” Cell Reports, vol. 35, no. 12. Cell Press, 2021.
ista: Contreras X, Amberg N, Davaatseren A, Hansen AH, Sonntag J, Andersen L, Bernthaler
T, Streicher C, Heger A-M, Johnson RL, Schwarz LA, Luo L, Rülicke T, Hippenmeyer
S. 2021. A genome-wide library of MADM mice for single-cell genetic mosaic analysis.
Cell Reports. 35(12), 109274.
mla: Contreras, Ximena, et al. “A Genome-Wide Library of MADM Mice for Single-Cell
Genetic Mosaic Analysis.” Cell Reports, vol. 35, no. 12, 109274, Cell Press,
2021, doi:10.1016/j.celrep.2021.109274.
short: X. Contreras, N. Amberg, A. Davaatseren, A.H. Hansen, J. Sonntag, L. Andersen,
T. Bernthaler, C. Streicher, A.-M. Heger, R.L. Johnson, L.A. Schwarz, L. Luo,
T. Rülicke, S. Hippenmeyer, Cell Reports 35 (2021).
date_created: 2021-06-27T22:01:48Z
date_published: 2021-06-22T00:00:00Z
date_updated: 2023-08-10T13:55:00Z
day: '22'
ddc:
- '570'
department:
- _id: SiHi
- _id: LoSw
- _id: PreCl
doi: 10.1016/j.celrep.2021.109274
ec_funded: 1
external_id:
isi:
- '000664463600016'
file:
- access_level: open_access
checksum: d49520fdcbbb5c2f883bddb67cee5d77
content_type: application/pdf
creator: asandaue
date_created: 2021-06-28T14:06:24Z
date_updated: 2021-06-28T14:06:24Z
file_id: '9613'
file_name: 2021_CellReports_Contreras.pdf
file_size: 7653149
relation: main_file
success: 1
file_date_updated: 2021-06-28T14:06:24Z
has_accepted_license: '1'
intvolume: ' 35'
isi: 1
issue: '12'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
project:
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular Mechanisms of Radial Neuronal Migration
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618444'
name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Cell Reports
publication_identifier:
eissn:
- '22111247'
publication_status: published
publisher: Cell Press
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/boost-for-mouse-genetic-analysis/
scopus_import: '1'
status: public
title: A genome-wide library of MADM mice for single-cell genetic mosaic analysis
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 35
year: '2021'
...
---
_id: '9906'
abstract:
- lang: eng
text: Endometriosis is a common gynecological disorder characterized by ectopic
growth of endometrium outside the uterus and is associated with chronic pain and
infertility. We investigated the role of the long intergenic noncoding RNA 01133
(LINC01133) in endometriosis, an lncRNA that has been implicated in several types
of cancer. We found that LINC01133 is upregulated in ectopic endometriotic lesions.
As expression appeared higher in the epithelial endometrial layer, we performed
a siRNA knockdown of LINC01133 in an endometriosis epithelial cell line. Phenotypic
assays indicated that LINC01133 may promote proliferation and suppress cellular
migration, and affect the cytoskeleton and morphology of the cells. Gene ontology
analysis of differentially expressed genes indicated that cell proliferation and
migration pathways were affected in line with the observed phenotype. We validated
upregulation of p21 and downregulation of Cyclin A at the protein level, which
together with the quantification of the DNA content using fluorescence-activated
cell sorting (FACS) analysis indicated that the observed effects on cellular proliferation
may be due to changes in cell cycle. Further, we found testis-specific protein
kinase 1 (TESK1) kinase upregulation corresponding with phosphorylation and inactivation
of actin severing protein Cofilin, which could explain changes in the cytoskeleton
and cellular migration. These results indicate that endometriosis is associated
with LINC01133 upregulation, which may affect pathogenesis via the cellular proliferation
and migration pathways.
acknowledgement: "Open access funding provided by Medical University of Vienna. The
authors would like to thank all the participants and health professionals involved
in the present study. We want to thank our technical assistants Barbara Widmar and
Matthias Witzmann-Stern for their diligent work and constant assistance. We would
like to thank Simon Hippenmeyer for access to\r\nbioinformatic infrastructure and
resources."
article_number: '8385'
article_processing_charge: Yes
article_type: original
author:
- first_name: Iveta
full_name: Yotova, Iveta
last_name: Yotova
- first_name: Quanah J.
full_name: Hudson, Quanah J.
last_name: Hudson
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Katharina
full_name: Proestling, Katharina
last_name: Proestling
- first_name: Isabella
full_name: Haslinger, Isabella
last_name: Haslinger
- first_name: Lorenz
full_name: Kuessel, Lorenz
last_name: Kuessel
- first_name: Alexandra
full_name: Perricos, Alexandra
last_name: Perricos
- first_name: Heinrich
full_name: Husslein, Heinrich
last_name: Husslein
- first_name: René
full_name: Wenzl, René
last_name: Wenzl
citation:
ama: Yotova I, Hudson QJ, Pauler F, et al. LINC01133 inhibits invasion and promotes
proliferation in an endometriosis epithelial cell line. International Journal
of Molecular Sciences. 2021;22(16). doi:10.3390/ijms22168385
apa: Yotova, I., Hudson, Q. J., Pauler, F., Proestling, K., Haslinger, I., Kuessel,
L., … Wenzl, R. (2021). LINC01133 inhibits invasion and promotes proliferation
in an endometriosis epithelial cell line. International Journal of Molecular
Sciences. MDPI. https://doi.org/10.3390/ijms22168385
chicago: Yotova, Iveta, Quanah J. Hudson, Florian Pauler, Katharina Proestling,
Isabella Haslinger, Lorenz Kuessel, Alexandra Perricos, Heinrich Husslein, and
René Wenzl. “LINC01133 Inhibits Invasion and Promotes Proliferation in an Endometriosis
Epithelial Cell Line.” International Journal of Molecular Sciences. MDPI,
2021. https://doi.org/10.3390/ijms22168385.
ieee: I. Yotova et al., “LINC01133 inhibits invasion and promotes proliferation
in an endometriosis epithelial cell line,” International Journal of Molecular
Sciences, vol. 22, no. 16. MDPI, 2021.
ista: Yotova I, Hudson QJ, Pauler F, Proestling K, Haslinger I, Kuessel L, Perricos
A, Husslein H, Wenzl R. 2021. LINC01133 inhibits invasion and promotes proliferation
in an endometriosis epithelial cell line. International Journal of Molecular Sciences.
22(16), 8385.
mla: Yotova, Iveta, et al. “LINC01133 Inhibits Invasion and Promotes Proliferation
in an Endometriosis Epithelial Cell Line.” International Journal of Molecular
Sciences, vol. 22, no. 16, 8385, MDPI, 2021, doi:10.3390/ijms22168385.
short: I. Yotova, Q.J. Hudson, F. Pauler, K. Proestling, I. Haslinger, L. Kuessel,
A. Perricos, H. Husslein, R. Wenzl, International Journal of Molecular Sciences
22 (2021).
date_created: 2021-08-15T22:01:27Z
date_published: 2021-08-04T00:00:00Z
date_updated: 2023-08-11T10:34:13Z
day: '04'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.3390/ijms22168385
external_id:
isi:
- '000689147400001'
file:
- access_level: open_access
checksum: be7f0042607ca60549cb27513c19c6af
content_type: application/pdf
creator: asandaue
date_created: 2021-08-16T09:29:17Z
date_updated: 2021-08-16T09:29:17Z
file_id: '9922'
file_name: 2021_InternationalJournalOfMolecularSciences_Yotova.pdf
file_size: 2646018
relation: main_file
success: 1
file_date_updated: 2021-08-16T09:29:17Z
has_accepted_license: '1'
intvolume: ' 22'
isi: 1
issue: '16'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
publication: International Journal of Molecular Sciences
publication_identifier:
eissn:
- '14220067'
issn:
- '16616596'
publication_status: published
publisher: MDPI
quality_controlled: '1'
scopus_import: '1'
status: public
title: LINC01133 inhibits invasion and promotes proliferation in an endometriosis
epithelial cell line
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 22
year: '2021'
...
---
_id: '9073'
abstract:
- lang: eng
text: The sensory and cognitive abilities of the mammalian neocortex are underpinned
by intricate columnar and laminar circuits formed from an array of diverse neuronal
populations. One approach to determining how interactions between these circuit
components give rise to complex behavior is to investigate the rules by which
cortical circuits are formed and acquire functionality during development. This
review summarizes recent research on the development of the neocortex, from genetic
determination in neural stem cells through to the dynamic role that specific neuronal
populations play in the earliest circuits of neocortex, and how they contribute
to emergent function and cognition. While many of these endeavors take advantage
of model systems, consideration will also be given to advances in our understanding
of activity in nascent human circuits. Such cross-species perspective is imperative
when investigating the mechanisms underlying the dysfunction of early neocortical
circuits in neurodevelopmental disorders, so that one can identify targets amenable
to therapeutic intervention.
acknowledgement: Work in the I.L.H.-O. laboratory was supported by European Research
Council Grant ERC-2015-CoG 681577 and German Research Foundation Ha 4466/10-1, Ha4466/11-1,
Ha4466/12-1, SPP 1665, and SFB 936B5. Work in the S.J.B.B. laboratory was supported
by Biotechnology and Biological Sciences Research Council BB/P003796/1, Medical
Research Council MR/K004387/1 and MR/T033320/1, Wellcome Trust 215199/Z/19/Z and
102386/Z/13/Z, and John Fell Fund. Work in the S.H. laboratory was supported by
European Research Council Grants ERC-2016-CoG 725780 LinPro and FWF SFB F78. This
work was supported by National Institutes of Health Grant NIMH 1R01MH110553 to N.V.D.M.G.
Work in the J.A.C. laboratory was supported by the Ludwig Family Foundation, Simons
Foundation SFARI Research Award, and National Institutes of Health/National Institute
of Mental Health R01 MH102365 and R01MH113852. The B.V. laboratory was supported
by Whitehall Foundation 2017-12-73, National Science Foundation 1736028, National
Institutes of Health, National Institute of General Medical Sciences R01GM134363-01,
and Halıcıoğlu Data Science Institute Fellowship. This work was supported by the
University of California San Diego School of Medicine.
article_processing_charge: No
article_type: original
author:
- first_name: Ileana L.
full_name: Hanganu-Opatz, Ileana L.
last_name: Hanganu-Opatz
- first_name: Simon J. B.
full_name: Butt, Simon J. B.
last_name: Butt
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Natalia V.
full_name: De Marco García, Natalia V.
last_name: De Marco García
- first_name: Jessica A.
full_name: Cardin, Jessica A.
last_name: Cardin
- first_name: Bradley
full_name: Voytek, Bradley
last_name: Voytek
- first_name: Alysson R.
full_name: Muotri, Alysson R.
last_name: Muotri
citation:
ama: Hanganu-Opatz IL, Butt SJB, Hippenmeyer S, et al. The logic of developing neocortical
circuits in health and disease. The Journal of Neuroscience. 2021;41(5):813-822.
doi:10.1523/jneurosci.1655-20.2020
apa: Hanganu-Opatz, I. L., Butt, S. J. B., Hippenmeyer, S., De Marco García, N.
V., Cardin, J. A., Voytek, B., & Muotri, A. R. (2021). The logic of developing
neocortical circuits in health and disease. The Journal of Neuroscience.
Society for Neuroscience. https://doi.org/10.1523/jneurosci.1655-20.2020
chicago: Hanganu-Opatz, Ileana L., Simon J. B. Butt, Simon Hippenmeyer, Natalia
V. De Marco García, Jessica A. Cardin, Bradley Voytek, and Alysson R. Muotri.
“The Logic of Developing Neocortical Circuits in Health and Disease.” The Journal
of Neuroscience. Society for Neuroscience, 2021. https://doi.org/10.1523/jneurosci.1655-20.2020.
ieee: I. L. Hanganu-Opatz et al., “The logic of developing neocortical circuits
in health and disease,” The Journal of Neuroscience, vol. 41, no. 5. Society
for Neuroscience, pp. 813–822, 2021.
ista: Hanganu-Opatz IL, Butt SJB, Hippenmeyer S, De Marco García NV, Cardin JA,
Voytek B, Muotri AR. 2021. The logic of developing neocortical circuits in health
and disease. The Journal of Neuroscience. 41(5), 813–822.
mla: Hanganu-Opatz, Ileana L., et al. “The Logic of Developing Neocortical Circuits
in Health and Disease.” The Journal of Neuroscience, vol. 41, no. 5, Society
for Neuroscience, 2021, pp. 813–22, doi:10.1523/jneurosci.1655-20.2020.
short: I.L. Hanganu-Opatz, S.J.B. Butt, S. Hippenmeyer, N.V. De Marco García, J.A.
Cardin, B. Voytek, A.R. Muotri, The Journal of Neuroscience 41 (2021) 813–822.
date_created: 2021-02-03T12:23:51Z
date_published: 2021-02-03T00:00:00Z
date_updated: 2023-09-05T14:03:17Z
day: '03'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1523/jneurosci.1655-20.2020
ec_funded: 1
external_id:
isi:
- '000616763400002'
pmid:
- '33431633'
file:
- access_level: open_access
checksum: 578fd7ed1a0aef74bce61bea2d987b33
content_type: application/pdf
creator: dernst
date_created: 2022-05-27T06:59:55Z
date_updated: 2022-05-27T06:59:55Z
file_id: '11414'
file_name: 2021_JourNeuroscience_Hanganu.pdf
file_size: 1031150
relation: main_file
success: 1
file_date_updated: 2022-05-27T06:59:55Z
has_accepted_license: '1'
intvolume: ' 41'
isi: 1
issue: '5'
keyword:
- General Neuroscience
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: 813-822
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F07805
name: Molecular Mechanisms of Neural Stem Cell Lineage Progression
publication: The Journal of Neuroscience
publication_identifier:
eissn:
- 1529-2401
issn:
- 0270-6474
publication_status: published
publisher: Society for Neuroscience
quality_controlled: '1'
scopus_import: '1'
status: public
title: The logic of developing neocortical circuits in health and disease
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 41
year: '2021'
...
---
_id: '9793'
abstract:
- lang: eng
text: Astrocytes extensively infiltrate the neuropil to regulate critical aspects
of synaptic development and function. This process is regulated by transcellular
interactions between astrocytes and neurons via cell adhesion molecules. How astrocytes
coordinate developmental processes among one another to parse out the synaptic
neuropil and form non-overlapping territories is unknown. Here we identify a molecular
mechanism regulating astrocyte-astrocyte interactions during development to coordinate
astrocyte morphogenesis and gap junction coupling. We show that hepaCAM, a disease-linked,
astrocyte-enriched cell adhesion molecule, regulates astrocyte competition for
territory and morphological complexity in the developing mouse cortex. Furthermore,
conditional deletion of Hepacam from developing astrocytes significantly impairs
gap junction coupling between astrocytes and disrupts the balance between synaptic
excitation and inhibition. Mutations in HEPACAM cause megalencephalic leukoencephalopathy
with subcortical cysts in humans. Therefore, our findings suggest that disruption
of astrocyte self-organization mechanisms could be an underlying cause of neural
pathology.
acknowledgement: This work was supported by the National Institutes of Health (R01
DA047258 and R01 NS102237 to C.E., F32 NS100392 to K.T.B.) and the Holland-Trice
Brain Research Award (to C.E.). K.T.B. was supported by postdoctoral fellowships
from the Foerster-Bernstein Family and The Hartwell Foundation. The Hippenmeyer
lab was supported by the European Research Council (ERC) under the European Union’s
Horizon 2020 research and innovations program (725780 LinPro) to S.H. R.E. was supported
by Ministerio de Ciencia y Tecnología (RTI2018-093493-B-I00). We thank the Duke
Light Microscopy Core Facility, the Duke Transgenic Mouse Facility, Dr. U. Schulte
for assistance with proteomic experiments, and Dr. D. Silver for critical review
of the manuscript. Cartoon elements of figure panels were created using BioRender.com.
article_processing_charge: No
article_type: original
author:
- first_name: Katherine T.
full_name: Baldwin, Katherine T.
last_name: Baldwin
- first_name: Christabel X.
full_name: Tan, Christabel X.
last_name: Tan
- first_name: Samuel T.
full_name: Strader, Samuel T.
last_name: Strader
- first_name: Changyu
full_name: Jiang, Changyu
last_name: Jiang
- first_name: Justin T.
full_name: Savage, Justin T.
last_name: Savage
- first_name: Xabier
full_name: Elorza-Vidal, Xabier
last_name: Elorza-Vidal
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Raúl
full_name: Estévez, Raúl
last_name: Estévez
- first_name: Ru-Rong
full_name: Ji, Ru-Rong
last_name: Ji
- first_name: Cagla
full_name: Eroglu, Cagla
last_name: Eroglu
citation:
ama: Baldwin KT, Tan CX, Strader ST, et al. HepaCAM controls astrocyte self-organization
and coupling. Neuron. 2021;109(15):2427-2442.e10. doi:10.1016/j.neuron.2021.05.025
apa: Baldwin, K. T., Tan, C. X., Strader, S. T., Jiang, C., Savage, J. T., Elorza-Vidal,
X., … Eroglu, C. (2021). HepaCAM controls astrocyte self-organization and coupling.
Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2021.05.025
chicago: Baldwin, Katherine T., Christabel X. Tan, Samuel T. Strader, Changyu Jiang,
Justin T. Savage, Xabier Elorza-Vidal, Ximena Contreras, et al. “HepaCAM Controls
Astrocyte Self-Organization and Coupling.” Neuron. Elsevier, 2021. https://doi.org/10.1016/j.neuron.2021.05.025.
ieee: K. T. Baldwin et al., “HepaCAM controls astrocyte self-organization
and coupling,” Neuron, vol. 109, no. 15. Elsevier, p. 2427–2442.e10, 2021.
ista: Baldwin KT, Tan CX, Strader ST, Jiang C, Savage JT, Elorza-Vidal X, Contreras
X, Rülicke T, Hippenmeyer S, Estévez R, Ji R-R, Eroglu C. 2021. HepaCAM controls
astrocyte self-organization and coupling. Neuron. 109(15), 2427–2442.e10.
mla: Baldwin, Katherine T., et al. “HepaCAM Controls Astrocyte Self-Organization
and Coupling.” Neuron, vol. 109, no. 15, Elsevier, 2021, p. 2427–2442.e10,
doi:10.1016/j.neuron.2021.05.025.
short: K.T. Baldwin, C.X. Tan, S.T. Strader, C. Jiang, J.T. Savage, X. Elorza-Vidal,
X. Contreras, T. Rülicke, S. Hippenmeyer, R. Estévez, R.-R. Ji, C. Eroglu, Neuron
109 (2021) 2427–2442.e10.
date_created: 2021-08-06T09:08:25Z
date_published: 2021-08-04T00:00:00Z
date_updated: 2023-09-27T07:46:09Z
day: '04'
department:
- _id: SiHi
doi: 10.1016/j.neuron.2021.05.025
ec_funded: 1
external_id:
isi:
- '000692851900010'
pmid:
- '34171291'
intvolume: ' 109'
isi: 1
issue: '15'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.neuron.2021.05.025
month: '08'
oa: 1
oa_version: Published Version
page: 2427-2442.e10
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Neuron
publication_identifier:
eissn:
- 1097-4199
issn:
- 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: HepaCAM controls astrocyte self-organization and coupling
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 109
year: '2021'
...
---
_id: '10655'
abstract:
- lang: eng
text: "Adeno-associated viruses (AAVs) are widely used to deliver genetic material
in vivo to distinct cell types such as neurons or glial cells, allowing for targeted
manipulation. Transduction of microglia is mostly excluded from this strategy,
likely due to the cells’ heterogeneous state upon environmental changes, which
makes AAV design challenging. Here, we established the retina as a model system
for microglial AAV validation and optimization. First, we show that AAV2/6 transduced
microglia in both synaptic layers, where layer preference corresponds to the intravitreal
or subretinal delivery method. Surprisingly, we observed significantly enhanced
microglial transduction during photoreceptor degeneration. Thus, we modified the
AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E,
R576Q, K493S, and K459S), resulting in increased microglial transduction in the
outer plexiform layer. Finally, to improve microglial-specific transduction, we
validated a Cre-dependent transgene delivery cassette for use in combination with
the Cx3cr1CreERT2 mouse line. Together, our results provide a foundation for future
studies optimizing AAV-mediated microglia transduction and highlight that environmental
conditions influence microglial transduction efficiency.\r\n"
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: This project has received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation programme
(grant agreement no. 715571). The research was supported by the Scientific Service
Units (SSU) of IST Austria through resources provided by the Bioimaging Facility,
the Life Science Facility, and the Pre-Clinical Facility, namely Sonja Haslinger
and Michael Schunn for their animal colony management and support. We would also
like to thank Chakrabarty Lab for sharing the plasmids for AAV2/6 production. Finally,
we would like to thank the Siegert team members for discussion about the manuscript.
article_processing_charge: Yes
article_type: original
author:
- first_name: Margaret E
full_name: Maes, Margaret E
id: 3838F452-F248-11E8-B48F-1D18A9856A87
last_name: Maes
orcid: 0000-0001-9642-1085
- first_name: Gabriele M.
full_name: Wögenstein, Gabriele M.
last_name: Wögenstein
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Raquel
full_name: Casado Polanco, Raquel
id: 15240fc1-dbcd-11ea-9d1d-ac5a786425fd
last_name: Casado Polanco
orcid: 0000-0001-8293-4568
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. Optimizing
AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor
degenerative environment. Molecular Therapy - Methods and Clinical Development.
2021;23:210-224. doi:10.1016/j.omtm.2021.09.006
apa: Maes, M. E., Wögenstein, G. M., Colombo, G., Casado Polanco, R., & Siegert,
S. (2021). Optimizing AAV2/6 microglial targeting identified enhanced efficiency
in the photoreceptor degenerative environment. Molecular Therapy - Methods
and Clinical Development. Elsevier. https://doi.org/10.1016/j.omtm.2021.09.006
chicago: Maes, Margaret E, Gabriele M. Wögenstein, Gloria Colombo, Raquel Casado
Polanco, and Sandra Siegert. “Optimizing AAV2/6 Microglial Targeting Identified
Enhanced Efficiency in the Photoreceptor Degenerative Environment.” Molecular
Therapy - Methods and Clinical Development. Elsevier, 2021. https://doi.org/10.1016/j.omtm.2021.09.006.
ieee: M. E. Maes, G. M. Wögenstein, G. Colombo, R. Casado Polanco, and S. Siegert,
“Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the
photoreceptor degenerative environment,” Molecular Therapy - Methods and Clinical
Development, vol. 23. Elsevier, pp. 210–224, 2021.
ista: Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. 2021. Optimizing
AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor
degenerative environment. Molecular Therapy - Methods and Clinical Development.
23, 210–224.
mla: Maes, Margaret E., et al. “Optimizing AAV2/6 Microglial Targeting Identified
Enhanced Efficiency in the Photoreceptor Degenerative Environment.” Molecular
Therapy - Methods and Clinical Development, vol. 23, Elsevier, 2021, pp. 210–24,
doi:10.1016/j.omtm.2021.09.006.
short: M.E. Maes, G.M. Wögenstein, G. Colombo, R. Casado Polanco, S. Siegert, Molecular
Therapy - Methods and Clinical Development 23 (2021) 210–224.
date_created: 2022-01-23T23:01:28Z
date_published: 2021-12-10T00:00:00Z
date_updated: 2023-11-16T13:12:03Z
day: '10'
ddc:
- '570'
department:
- _id: SaSi
- _id: SiHi
doi: 10.1016/j.omtm.2021.09.006
ec_funded: 1
external_id:
isi:
- '000748748500019'
file:
- access_level: open_access
checksum: 77dc540e8011c5475031bdf6ccef20a6
content_type: application/pdf
creator: cchlebak
date_created: 2022-01-24T07:43:09Z
date_updated: 2022-01-24T07:43:09Z
file_id: '10657'
file_name: 2021_MolTherMethodsClinDev_Maes.pdf
file_size: 4794147
relation: main_file
success: 1
file_date_updated: 2022-01-24T07:43:09Z
has_accepted_license: '1'
intvolume: ' 23'
isi: 1
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 210-224
project:
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
publication: Molecular Therapy - Methods and Clinical Development
publication_identifier:
eissn:
- 2329-0501
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the
photoreceptor degenerative environment
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 23
year: '2021'
...
---
_id: '10321'
abstract:
- lang: eng
text: Mosaic analysis with double markers (MADM) technology enables the generation
of genetic mosaic tissue in mice. MADM enables concomitant fluorescent cell labeling
and introduction of a mutation of a gene of interest with single-cell resolution.
This protocol highlights major steps for the generation of genetic mosaic tissue
and the isolation and processing of respective tissues for downstream histological
analysis. For complete details on the use and execution of this protocol, please
refer to Contreras et al. (2021).
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: This research was supported by the Scientific Service Units (SSU)
at IST Austria through resources provided by the Bioimaging (BIF) and Preclinical
Facilities (PCF). We particularly thank Mohammad Goudarzi for assistance with photography
of mouse perfusion and dissection. N.A. received support from FWF Firnberg-Programm
(T 1031). This work was also supported by IST Austria institutional funds; FWF SFB
F78 to S.H.; and the European Research Council (ERC) under the European Union’s
Horizon 2020 research and innovation programme (grant agreement no. 725780 LinPro)
to S.H.
article_number: '100939'
article_processing_charge: Yes
article_type: original
author:
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Amberg N, Hippenmeyer S. Genetic mosaic dissection of candidate genes in mice
using mosaic analysis with double markers. STAR Protocols. 2021;2(4). doi:10.1016/j.xpro.2021.100939
apa: Amberg, N., & Hippenmeyer, S. (2021). Genetic mosaic dissection of candidate
genes in mice using mosaic analysis with double markers. STAR Protocols.
Cell Press. https://doi.org/10.1016/j.xpro.2021.100939
chicago: Amberg, Nicole, and Simon Hippenmeyer. “Genetic Mosaic Dissection of Candidate
Genes in Mice Using Mosaic Analysis with Double Markers.” STAR Protocols.
Cell Press, 2021. https://doi.org/10.1016/j.xpro.2021.100939.
ieee: N. Amberg and S. Hippenmeyer, “Genetic mosaic dissection of candidate genes
in mice using mosaic analysis with double markers,” STAR Protocols, vol.
2, no. 4. Cell Press, 2021.
ista: Amberg N, Hippenmeyer S. 2021. Genetic mosaic dissection of candidate genes
in mice using mosaic analysis with double markers. STAR Protocols. 2(4), 100939.
mla: Amberg, Nicole, and Simon Hippenmeyer. “Genetic Mosaic Dissection of Candidate
Genes in Mice Using Mosaic Analysis with Double Markers.” STAR Protocols,
vol. 2, no. 4, 100939, Cell Press, 2021, doi:10.1016/j.xpro.2021.100939.
short: N. Amberg, S. Hippenmeyer, STAR Protocols 2 (2021).
date_created: 2021-11-21T23:01:28Z
date_published: 2021-11-10T00:00:00Z
date_updated: 2023-11-16T13:08:03Z
day: '10'
ddc:
- '573'
department:
- _id: SiHi
doi: 10.1016/j.xpro.2021.100939
ec_funded: 1
file:
- access_level: open_access
checksum: 9e3f6d06bf583e7a8b6a9e9a60500a28
content_type: application/pdf
creator: cchlebak
date_created: 2021-11-22T08:23:58Z
date_updated: 2021-11-22T08:23:58Z
file_id: '10329'
file_name: 2021_STARProtocols_Amberg.pdf
file_size: 7309464
relation: main_file
success: 1
file_date_updated: 2021-11-22T08:23:58Z
has_accepted_license: '1'
intvolume: ' 2'
issue: '4'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T0101031
name: Role of Eed in neural stem cell lineage progression
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F07805
name: Molecular Mechanisms of Neural Stem Cell Lineage Progression
publication: STAR Protocols
publication_identifier:
eissn:
- 2666-1667
publication_status: published
publisher: Cell Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Genetic mosaic dissection of candidate genes in mice using mosaic analysis
with double markers
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 2
year: '2021'
...