---
_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
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'
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publication_identifier:
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quality_controlled: '1'
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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
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...
---
_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:
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- '000664463600016'
file:
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date_created: 2021-06-28T14:06:24Z
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language:
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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:
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(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
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...