---
_id: '7253'
abstract:
- lang: eng
text: The cyclin-dependent kinase inhibitor p57KIP2 is encoded by the imprinted
Cdkn1c locus, exhibits maternal expression, and is essential for cerebral cortex
development. How Cdkn1c regulates corticogenesis is however not clear. To this
end we employ Mosaic Analysis with Double Markers (MADM) technology to genetically
dissect Cdkn1c gene function in corticogenesis at single cell resolution. We find
that the previously described growth-inhibitory Cdkn1c function is a non-cell-autonomous
one, acting on the whole organism. In contrast we reveal a growth-promoting cell-autonomous
Cdkn1c function which at the mechanistic level mediates radial glial progenitor
cell and nascent projection neuron survival. Strikingly, the growth-promoting
function of Cdkn1c is highly dosage sensitive but not subject to genomic imprinting.
Collectively, our results suggest that the Cdkn1c locus regulates cortical development
through distinct cell-autonomous and non-cell-autonomous mechanisms. More generally,
our study highlights the importance to probe the relative contributions of cell
intrinsic gene function and tissue-wide mechanisms to the overall phenotype.
acknowledged_ssus:
- _id: PreCl
article_number: '195'
article_processing_charge: No
article_type: original
author:
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
orcid: 0000-0002-7903-3010
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Keiichi I.
full_name: Nakayama, Keiichi I.
last_name: Nakayama
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Laukoter S, Beattie RJ, Pauler F, Amberg N, Nakayama KI, Hippenmeyer S. Imprinted
Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex
development. Nature Communications. 2020;11. doi:10.1038/s41467-019-14077-2
apa: Laukoter, S., Beattie, R. J., Pauler, F., Amberg, N., Nakayama, K. I., &
Hippenmeyer, S. (2020). Imprinted Cdkn1c genomic locus cell-autonomously promotes
cell survival in cerebral cortex development. Nature Communications. Springer
Nature. https://doi.org/10.1038/s41467-019-14077-2
chicago: Laukoter, Susanne, Robert J Beattie, Florian Pauler, Nicole Amberg, Keiichi
I. Nakayama, and Simon Hippenmeyer. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously
Promotes Cell Survival in Cerebral Cortex Development.” Nature Communications.
Springer Nature, 2020. https://doi.org/10.1038/s41467-019-14077-2.
ieee: S. Laukoter, R. J. Beattie, F. Pauler, N. Amberg, K. I. Nakayama, and S. Hippenmeyer,
“Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral
cortex development,” Nature Communications, vol. 11. Springer Nature, 2020.
ista: Laukoter S, Beattie RJ, Pauler F, Amberg N, Nakayama KI, Hippenmeyer S. 2020.
Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral
cortex development. Nature Communications. 11, 195.
mla: Laukoter, Susanne, et al. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously
Promotes Cell Survival in Cerebral Cortex Development.” Nature Communications,
vol. 11, 195, Springer Nature, 2020, doi:10.1038/s41467-019-14077-2.
short: S. Laukoter, R.J. Beattie, F. Pauler, N. Amberg, K.I. Nakayama, S. Hippenmeyer,
Nature Communications 11 (2020).
date_created: 2020-01-11T10:42:48Z
date_published: 2020-01-10T00:00:00Z
date_updated: 2023-08-17T14:23:41Z
day: '10'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1038/s41467-019-14077-2
ec_funded: 1
external_id:
isi:
- '000551459000005'
file:
- access_level: open_access
checksum: ebf1ed522f4e0be8d94c939c1806a709
content_type: application/pdf
creator: dernst
date_created: 2020-01-13T07:42:31Z
date_updated: 2020-07-14T12:47:54Z
file_id: '7261'
file_name: 2020_NatureComm_Laukoter.pdf
file_size: 8063333
relation: main_file
file_date_updated: 2020-07-14T12:47:54Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '01'
oa: 1
oa_version: Published Version
project:
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T0101031
name: Role of Eed in neural stem cell lineage progression
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex
- _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: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/new-function-for-potential-tumour-suppressor-in-brain-development/
scopus_import: '1'
status: public
title: Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in
cerebral cortex development
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: 11
year: '2020'
...
---
_id: '7593'
abstract:
- lang: eng
text: Heterozygous loss of human PAFAH1B1 (coding for LIS1) results in the disruption
of neurogenesis and neuronal migration via dysregulation of microtubule (MT) stability
and dynein motor function/localization that alters mitotic spindle orientation,
chromosomal segregation, and nuclear migration. Recently, human induced pluripotent
stem cell (iPSC) models revealed an important role for LIS1 in controlling the
length of terminal cell divisions of outer radial glial (oRG) progenitors, suggesting
cellular functions of LIS1 in regulating neural progenitor cell (NPC) daughter
cell separation. Here we examined the late mitotic stages NPCs in vivo and mouse
embryonic fibroblasts (MEFs) in vitro from Pafah1b1-deficient mutants. Pafah1b1-deficient
neocortical NPCs and MEFs similarly exhibited cleavage plane displacement with
mislocalization of furrow-associated markers, associated with actomyosin dysfunction
and cell membrane hyper-contractility. Thus, it suggests LIS1 acts as a key molecular
link connecting MTs/dynein and actomyosin, ensuring that cell membrane contractility
is tightly controlled to execute proper daughter cell separation.
article_number: '51512'
article_processing_charge: No
article_type: original
author:
- first_name: Hyang Mi
full_name: Moon, Hyang Mi
last_name: Moon
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Liqun
full_name: Luo, Liqun
last_name: Luo
- first_name: Anthony
full_name: Wynshaw-Boris, Anthony
last_name: Wynshaw-Boris
citation:
ama: Moon HM, Hippenmeyer S, Luo L, Wynshaw-Boris A. LIS1 determines cleavage plane
positioning by regulating actomyosin-mediated cell membrane contractility. eLife.
2020;9. doi:10.7554/elife.51512
apa: Moon, H. M., Hippenmeyer, S., Luo, L., & Wynshaw-Boris, A. (2020). LIS1
determines cleavage plane positioning by regulating actomyosin-mediated cell membrane
contractility. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.51512
chicago: Moon, Hyang Mi, Simon Hippenmeyer, Liqun Luo, and Anthony Wynshaw-Boris.
“LIS1 Determines Cleavage Plane Positioning by Regulating Actomyosin-Mediated
Cell Membrane Contractility.” ELife. eLife Sciences Publications, 2020.
https://doi.org/10.7554/elife.51512.
ieee: H. M. Moon, S. Hippenmeyer, L. Luo, and A. Wynshaw-Boris, “LIS1 determines
cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility,”
eLife, vol. 9. eLife Sciences Publications, 2020.
ista: Moon HM, Hippenmeyer S, Luo L, Wynshaw-Boris A. 2020. LIS1 determines cleavage
plane positioning by regulating actomyosin-mediated cell membrane contractility.
eLife. 9, 51512.
mla: Moon, Hyang Mi, et al. “LIS1 Determines Cleavage Plane Positioning by Regulating
Actomyosin-Mediated Cell Membrane Contractility.” ELife, vol. 9, 51512,
eLife Sciences Publications, 2020, doi:10.7554/elife.51512.
short: H.M. Moon, S. Hippenmeyer, L. Luo, A. Wynshaw-Boris, ELife 9 (2020).
date_created: 2020-03-20T13:16:41Z
date_published: 2020-03-11T00:00:00Z
date_updated: 2023-08-18T07:06:31Z
day: '11'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.7554/elife.51512
external_id:
isi:
- '000522835800001'
pmid:
- '32159512'
file:
- access_level: open_access
checksum: 396ceb2dd10b102ef4e699666b9342c3
content_type: application/pdf
creator: dernst
date_created: 2020-09-24T07:03:20Z
date_updated: 2020-09-24T07:03:20Z
file_id: '8567'
file_name: 2020_elife_Moon.pdf
file_size: 15089438
relation: main_file
success: 1
file_date_updated: 2020-09-24T07:03:20Z
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/751958
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: LIS1 determines cleavage plane positioning by regulating actomyosin-mediated
cell membrane contractility
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: 9
year: '2020'
...
---
_id: '8093'
abstract:
- lang: eng
text: "Background: The activation of the EGFR/Ras-signalling pathway in tumour cells
induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment.\r\nMethods:
The effects of EGFR/Ras on the expression and translation of CCL20 were analysed
in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and
ELISA in vitro. CCL20 production was verified by immunohistochemistry in different
tumour tissues and correlated with clinical data. The effects of CCL20 on endothelial
cell migration and tumour-associated vascularisation were comprehensively analysed
with chemotaxis assays in vitro and in CCR6-deficient mice in vivo.\r\nResults:
Tumours facilitate progression by the EGFR/Ras-induced production of CCL20. Expression
of the chemokine CCL20 in tumours correlates with advanced tumour stage, increased
lymph node metastasis and decreased survival in patients. Microvascular endothelial
cells abundantly express the specific CCL20 receptor CCR6. CCR6 signalling in
endothelial cells induces angiogenesis. CCR6-deficient mice show significantly
decreased tumour growth and tumour-associated vascularisation. The observed phenotype
is dependent on CCR6 deficiency in stromal cells but not within the immune system.\r\nConclusion:
We propose that the chemokine axis CCL20–CCR6 represents a novel and promising
target to interfere with the tumour microenvironment, and opens an innovative
multimodal strategy for cancer therapy."
acknowledgement: "The authors would like to thank A. van Lierop for technical assistance.
In addition, we thank C. Dullin, J. Missbach-Güntner and S. Greco for advice and
assistance with fpVCT imaging. Furthermore, the authors would like to thank H. K.
Horst for advice on performing matrigel plug assays. This study has also been partially
presented in A. Schorr’s doctoral thesis and the funding report of the SPP 1190
‘The tumor-vessel interface’ of the ‘Deutsche Forschungsgemeinschaft’ (DFG).\r\nThis
project was funded by the SPP 1190 “The tumor-vessel interface” and HO 2092/8-1
of the ‘Deutsche Forschungsgemeinschaft’ (DFG) to B. Homey. In addition, it was
supported by grants from the Austrian Science Fund (FWF, W1212 to N. Amberg and
J. Klufa and I4300-B to T. Bauer), the WWTF project LS16-025 and the European Research
Council (ERC) Advanced grant (ERC-2015-AdG TNT-Tumors 694883) to M. Sibilia."
article_processing_charge: No
article_type: original
author:
- first_name: Andreas
full_name: Hippe, Andreas
last_name: Hippe
- first_name: Stephan Alexander
full_name: Braun, Stephan Alexander
last_name: Braun
- first_name: Péter
full_name: Oláh, Péter
last_name: Oláh
- first_name: Peter Arne
full_name: Gerber, Peter Arne
last_name: Gerber
- first_name: Anne
full_name: Schorr, Anne
last_name: Schorr
- first_name: Stephan
full_name: Seeliger, Stephan
last_name: Seeliger
- first_name: Stephanie
full_name: Holtz, Stephanie
last_name: Holtz
- first_name: Katharina
full_name: Jannasch, Katharina
last_name: Jannasch
- first_name: Andor
full_name: Pivarcsi, Andor
last_name: Pivarcsi
- first_name: Bettina
full_name: Buhren, Bettina
last_name: Buhren
- first_name: Holger
full_name: Schrumpf, Holger
last_name: Schrumpf
- first_name: Andreas
full_name: Kislat, Andreas
last_name: Kislat
- first_name: Erich
full_name: Bünemann, Erich
last_name: Bünemann
- first_name: Martin
full_name: Steinhoff, Martin
last_name: Steinhoff
- first_name: Jens
full_name: Fischer, Jens
last_name: Fischer
- first_name: Sérgio A.
full_name: Lira, Sérgio A.
last_name: Lira
- first_name: Petra
full_name: Boukamp, Petra
last_name: Boukamp
- first_name: Peter
full_name: Hevezi, Peter
last_name: Hevezi
- first_name: Nikolas Hendrik
full_name: Stoecklein, Nikolas Hendrik
last_name: Stoecklein
- first_name: Thomas
full_name: Hoffmann, Thomas
last_name: Hoffmann
- first_name: Frauke
full_name: Alves, Frauke
last_name: Alves
- first_name: Jonathan
full_name: Sleeman, Jonathan
last_name: Sleeman
- first_name: Thomas
full_name: Bauer, Thomas
last_name: Bauer
- first_name: Jörg
full_name: Klufa, Jörg
last_name: Klufa
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Maria
full_name: Sibilia, Maria
last_name: Sibilia
- first_name: Albert
full_name: Zlotnik, Albert
last_name: Zlotnik
- first_name: Anja
full_name: Müller-Homey, Anja
last_name: Müller-Homey
- first_name: Bernhard
full_name: Homey, Bernhard
last_name: Homey
citation:
ama: Hippe A, Braun SA, Oláh P, et al. EGFR/Ras-induced CCL20 production modulates
the tumour microenvironment. British Journal of Cancer. 2020;123:942-954.
doi:10.1038/s41416-020-0943-2
apa: Hippe, A., Braun, S. A., Oláh, P., Gerber, P. A., Schorr, A., Seeliger, S.,
… Homey, B. (2020). EGFR/Ras-induced CCL20 production modulates the tumour microenvironment.
British Journal of Cancer. Springer Nature. https://doi.org/10.1038/s41416-020-0943-2
chicago: Hippe, Andreas, Stephan Alexander Braun, Péter Oláh, Peter Arne Gerber,
Anne Schorr, Stephan Seeliger, Stephanie Holtz, et al. “EGFR/Ras-Induced CCL20
Production Modulates the Tumour Microenvironment.” British Journal of Cancer.
Springer Nature, 2020. https://doi.org/10.1038/s41416-020-0943-2.
ieee: A. Hippe et al., “EGFR/Ras-induced CCL20 production modulates the tumour
microenvironment,” British Journal of Cancer, vol. 123. Springer Nature,
pp. 942–954, 2020.
ista: Hippe A, Braun SA, Oláh P, Gerber PA, Schorr A, Seeliger S, Holtz S, Jannasch
K, Pivarcsi A, Buhren B, Schrumpf H, Kislat A, Bünemann E, Steinhoff M, Fischer
J, Lira SA, Boukamp P, Hevezi P, Stoecklein NH, Hoffmann T, Alves F, Sleeman J,
Bauer T, Klufa J, Amberg N, Sibilia M, Zlotnik A, Müller-Homey A, Homey B. 2020.
EGFR/Ras-induced CCL20 production modulates the tumour microenvironment. British
Journal of Cancer. 123, 942–954.
mla: Hippe, Andreas, et al. “EGFR/Ras-Induced CCL20 Production Modulates the Tumour
Microenvironment.” British Journal of Cancer, vol. 123, Springer Nature,
2020, pp. 942–54, doi:10.1038/s41416-020-0943-2.
short: A. Hippe, S.A. Braun, P. Oláh, P.A. Gerber, A. Schorr, S. Seeliger, S. Holtz,
K. Jannasch, A. Pivarcsi, B. Buhren, H. Schrumpf, A. Kislat, E. Bünemann, M. Steinhoff,
J. Fischer, S.A. Lira, P. Boukamp, P. Hevezi, N.H. Stoecklein, T. Hoffmann, F.
Alves, J. Sleeman, T. Bauer, J. Klufa, N. Amberg, M. Sibilia, A. Zlotnik, A. Müller-Homey,
B. Homey, British Journal of Cancer 123 (2020) 942–954.
date_created: 2020-07-05T22:00:46Z
date_published: 2020-09-15T00:00:00Z
date_updated: 2023-08-22T07:51:12Z
day: '15'
ddc:
- '610'
department:
- _id: SiHi
doi: 10.1038/s41416-020-0943-2
external_id:
isi:
- '000544152500001'
pmid:
- '32601464'
file:
- access_level: open_access
checksum: 05a8e65d49c3f5b8e37ac4afe68287e2
content_type: application/pdf
creator: cchlebak
date_created: 2021-12-02T12:35:12Z
date_updated: 2021-12-02T12:35:12Z
file_id: '10398'
file_name: 2020_BrJournalCancer_Hippe.pdf
file_size: 3620691
relation: main_file
success: 1
file_date_updated: 2021-12-02T12:35:12Z
has_accepted_license: '1'
intvolume: ' 123'
isi: 1
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: 942-954
pmid: 1
publication: British Journal of Cancer
publication_identifier:
eissn:
- 1532-1827
issn:
- 0007-0920
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: erratum
url: https://doi.org/10.1038/s41416-021-01563-y
record:
- id: '10170'
relation: later_version
status: deleted
scopus_import: '1'
status: public
title: EGFR/Ras-induced CCL20 production modulates the tumour microenvironment
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: 123
year: '2020'
...
---
_id: '8162'
abstract:
- lang: eng
text: In mammalian genomes, a subset of genes is regulated by genomic imprinting,
resulting in silencing of one parental allele. Imprinting is essential for cerebral
cortex development, but prevalence and functional impact in individual cells is
unclear. Here, we determined allelic expression in cortical cell types and established
a quantitative platform to interrogate imprinting in single cells. We created
cells with uniparental chromosome disomy (UPD) containing two copies of either
the maternal or the paternal chromosome; hence, imprinted genes will be 2-fold
overexpressed or not expressed. By genetic labeling of UPD, we determined cellular
phenotypes and transcriptional responses to deregulated imprinted gene expression
at unprecedented single-cell resolution. We discovered an unexpected degree of
cell-type specificity and a novel function of imprinting in the regulation of
cortical astrocyte survival. More generally, our results suggest functional relevance
of imprinted gene expression in glial astrocyte lineage and thus for generating
cortical cell-type diversity.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and
C. Czepe (VBCF GmbH, NGS Unit), and A. Seitz and P. Moll (Lexogen GmbH) for technical
support; G. Arque, S. Resch, C. Igler, C. Dotter, C. Yahya, Q. Hudson, and D. Andergassen
for initial experiments and/or assistance; D. Barlow, O. Bell, and all members of
the Hippenmeyer lab for discussion; and N. Barton, B. Vicoso, M. Sixt, and L. Luo
for comments on earlier versions of the manuscript. This research was supported
by the Scientific Service Units (SSU) of IST Austria through resources provided
by the Bioimaging Facilities (BIF), Life Science Facilities (LSF), and Preclinical
Facilities (PCF). A.H.H. is a recipient of a DOC fellowship (24812) of the Austrian
Academy of Sciences. N.A. received support from the FWF Firnberg-Programm (T 1031).
R.B. received support from the FWF Meitner-Programm (M 2416). This work was also
supported by IST Austria institutional funds; a NÖ Forschung und Bildung n[f+b]
life science call grant (C13-002) to S.H.; a program grant from the Human Frontiers
Science Program (RGP0053/2014) to S.H.; the People Programme (Marie Curie Actions)
of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant
agreement 618444 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_processing_charge: No
article_type: original
author:
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
orcid: 0000-0002-7903-3010
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- 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: Thomas
full_name: Penz, Thomas
last_name: Penz
- first_name: Christoph
full_name: Bock, Christoph
last_name: Bock
orcid: 0000-0001-6091-3088
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Laukoter S, Pauler F, Beattie RJ, et al. Cell-type specificity of genomic imprinting
in cerebral cortex. Neuron. 2020;107(6):1160-1179.e9. doi:10.1016/j.neuron.2020.06.031
apa: Laukoter, S., Pauler, F., Beattie, R. J., Amberg, N., Hansen, A. H., Streicher,
C., … Hippenmeyer, S. (2020). Cell-type specificity of genomic imprinting in cerebral
cortex. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.06.031
chicago: Laukoter, Susanne, Florian Pauler, Robert J Beattie, Nicole Amberg, Andi
H Hansen, Carmen Streicher, Thomas Penz, Christoph Bock, and Simon Hippenmeyer.
“Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” Neuron.
Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.06.031.
ieee: S. Laukoter et al., “Cell-type specificity of genomic imprinting in
cerebral cortex,” Neuron, vol. 107, no. 6. Elsevier, p. 1160–1179.e9, 2020.
ista: Laukoter S, Pauler F, Beattie RJ, Amberg N, Hansen AH, Streicher C, Penz T,
Bock C, Hippenmeyer S. 2020. Cell-type specificity of genomic imprinting in cerebral
cortex. Neuron. 107(6), 1160–1179.e9.
mla: Laukoter, Susanne, et al. “Cell-Type Specificity of Genomic Imprinting in Cerebral
Cortex.” Neuron, vol. 107, no. 6, Elsevier, 2020, p. 1160–1179.e9, doi:10.1016/j.neuron.2020.06.031.
short: S. Laukoter, F. Pauler, R.J. Beattie, N. Amberg, A.H. Hansen, C. Streicher,
T. Penz, C. Bock, S. Hippenmeyer, Neuron 107 (2020) 1160–1179.e9.
date_created: 2020-07-23T16:03:12Z
date_published: 2020-09-23T00:00:00Z
date_updated: 2023-08-22T08:20:11Z
day: '23'
ddc:
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publication: Neuron
publication_identifier:
issn:
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publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on IST Website
relation: press_release
url: https://ist.ac.at/en/news/cells-react-differently-to-genomic-imprinting/
scopus_import: '1'
status: public
title: Cell-type specificity of genomic imprinting in cerebral cortex
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legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
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short: CC BY-NC-ND (4.0)
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...
---
_id: '8592'
abstract:
- lang: eng
text: Glioblastoma is the most malignant cancer in the brain and currently incurable.
It is urgent to identify effective targets for this lethal disease. Inhibition
of such targets should suppress the growth of cancer cells and, ideally also precancerous
cells for early prevention, but minimally affect their normal counterparts. Using
genetic mouse models with neural stem cells (NSCs) or oligodendrocyte precursor
cells (OPCs) as the cells‐of‐origin/mutation, it is shown that the susceptibility
of cells within the development hierarchy of glioma to the knockout of insulin‐like
growth factor I receptor (IGF1R) is determined not only by their oncogenic states,
but also by their cell identities/states. Knockout of IGF1R selectively disrupts
the growth of mutant and transformed, but not normal OPCs, or NSCs. The desirable
outcome of IGF1R knockout on cell growth requires the mutant cells to commit to
the OPC identity regardless of its development hierarchical status. At the molecular
level, oncogenic mutations reprogram the cellular network of OPCs and force them
to depend more on IGF1R for their growth. A new‐generation brain‐penetrable, orally
available IGF1R inhibitor harnessing tumor OPCs in the brain is also developed.
The findings reveal the cellular window of IGF1R targeting and establish IGF1R
as an effective target for the prevention and treatment of glioblastoma.
acknowledgement: The authors thank Drs. J. Eisen, QR. Lu, S. Duan, Z‐H. Li, W. Mo,
and Q. Wu for their critical comments on the manuscript. They also thank Dr. H.
Zong for providing the CKO_NG2‐CreER model. This work is supported by the National
Key Research and Development Program of China, Stem Cell and Translational Research
(2016YFA0101201 to C.L., 2016YFA0100303 to Y.J.W.), the National Natural Science
Foundation of China (81673035 and 81972915 to C.L., 81472722 to Y.J.W.), the Science
Foundation for Distinguished Young Scientists of Zhejiang Province (LR17H160001
to C.L.), Fundamental Research Funds for the Central Universities (2016QNA7023 and
2017QNA7028 to C.L.) and the Thousand Talent Program for Young Outstanding Scientists,
China (to C.L.), IST Austria institutional funds (to S.H.), European Research Council
(ERC) under the European Union's Horizon 2020 research and innovation programme
(725780 LinPro to S.H.). C.L. is a scholar of K. C. Wong Education Foundation.
article_number: '2001724'
article_processing_charge: No
article_type: original
author:
- first_name: Anhao
full_name: Tian, Anhao
last_name: Tian
- first_name: Bo
full_name: Kang, Bo
last_name: Kang
- first_name: Baizhou
full_name: Li, Baizhou
last_name: Li
- first_name: Biying
full_name: Qiu, Biying
last_name: Qiu
- first_name: Wenhong
full_name: Jiang, Wenhong
last_name: Jiang
- first_name: Fangjie
full_name: Shao, Fangjie
last_name: Shao
- first_name: Qingqing
full_name: Gao, Qingqing
last_name: Gao
- first_name: Rui
full_name: Liu, Rui
last_name: Liu
- first_name: Chengwei
full_name: Cai, Chengwei
last_name: Cai
- first_name: Rui
full_name: Jing, Rui
last_name: Jing
- first_name: Wei
full_name: Wang, Wei
last_name: Wang
- first_name: Pengxiang
full_name: Chen, Pengxiang
last_name: Chen
- first_name: Qinghui
full_name: Liang, Qinghui
last_name: Liang
- first_name: Lili
full_name: Bao, Lili
last_name: Bao
- first_name: Jianghong
full_name: Man, Jianghong
last_name: Man
- first_name: Yan
full_name: Wang, Yan
last_name: Wang
- first_name: Yu
full_name: Shi, Yu
last_name: Shi
- first_name: Jin
full_name: Li, Jin
last_name: Li
- first_name: Minmin
full_name: Yang, Minmin
last_name: Yang
- first_name: Lisha
full_name: Wang, Lisha
last_name: Wang
- first_name: Jianmin
full_name: Zhang, Jianmin
last_name: Zhang
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Junming
full_name: Zhu, Junming
last_name: Zhu
- first_name: Xiuwu
full_name: Bian, Xiuwu
last_name: Bian
- first_name: Ying‐Jie
full_name: Wang, Ying‐Jie
last_name: Wang
- first_name: Chong
full_name: Liu, Chong
last_name: Liu
citation:
ama: Tian A, Kang B, Li B, et al. Oncogenic state and cell identity combinatorially
dictate the susceptibility of cells within glioma development hierarchy to IGF1R
targeting. Advanced Science. 2020;7(21). doi:10.1002/advs.202001724
apa: Tian, A., Kang, B., Li, B., Qiu, B., Jiang, W., Shao, F., … Liu, C. (2020).
Oncogenic state and cell identity combinatorially dictate the susceptibility of
cells within glioma development hierarchy to IGF1R targeting. Advanced Science.
Wiley. https://doi.org/10.1002/advs.202001724
chicago: Tian, Anhao, Bo Kang, Baizhou Li, Biying Qiu, Wenhong Jiang, Fangjie Shao,
Qingqing Gao, et al. “Oncogenic State and Cell Identity Combinatorially Dictate
the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting.”
Advanced Science. Wiley, 2020. https://doi.org/10.1002/advs.202001724.
ieee: A. Tian et al., “Oncogenic state and cell identity combinatorially
dictate the susceptibility of cells within glioma development hierarchy to IGF1R
targeting,” Advanced Science, vol. 7, no. 21. Wiley, 2020.
ista: Tian A, Kang B, Li B, Qiu B, Jiang W, Shao F, Gao Q, Liu R, Cai C, Jing R,
Wang W, Chen P, Liang Q, Bao L, Man J, Wang Y, Shi Y, Li J, Yang M, Wang L, Zhang
J, Hippenmeyer S, Zhu J, Bian X, Wang Y, Liu C. 2020. Oncogenic state and cell
identity combinatorially dictate the susceptibility of cells within glioma development
hierarchy to IGF1R targeting. Advanced Science. 7(21), 2001724.
mla: Tian, Anhao, et al. “Oncogenic State and Cell Identity Combinatorially Dictate
the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting.”
Advanced Science, vol. 7, no. 21, 2001724, Wiley, 2020, doi:10.1002/advs.202001724.
short: A. Tian, B. Kang, B. Li, B. Qiu, W. Jiang, F. Shao, Q. Gao, R. Liu, C. Cai,
R. Jing, W. Wang, P. Chen, Q. Liang, L. Bao, J. Man, Y. Wang, Y. Shi, J. Li, M.
Yang, L. Wang, J. Zhang, S. Hippenmeyer, J. Zhu, X. Bian, Y. Wang, C. Liu, Advanced
Science 7 (2020).
date_created: 2020-10-01T09:44:13Z
date_published: 2020-11-04T00:00:00Z
date_updated: 2023-08-22T09:53:01Z
day: '04'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1002/advs.202001724
ec_funded: 1
external_id:
isi:
- '000573860700001'
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content_type: application/pdf
creator: dernst
date_created: 2020-12-10T14:07:24Z
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success: 1
file_date_updated: 2020-12-10T14:07:24Z
has_accepted_license: '1'
intvolume: ' 7'
isi: 1
issue: '21'
keyword:
- General Engineering
- General Physics and Astronomy
- General Materials Science
- Medicine (miscellaneous)
- General Chemical Engineering
- Biochemistry
- Genetics and Molecular Biology (miscellaneous)
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
publication: Advanced Science
publication_identifier:
issn:
- 2198-3844
publication_status: published
publisher: Wiley
quality_controlled: '1'
status: public
title: Oncogenic state and cell identity combinatorially dictate the susceptibility
of cells within glioma development hierarchy to IGF1R targeting
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: 7
year: '2020'
...