---
_id: '11478'
abstract:
- lang: eng
text: Cerebral organoids differentiated from human-induced pluripotent stem cells
(hiPSC) provide a unique opportunity to investigate brain development. However,
organoids usually lack microglia, brain-resident immune cells, which are present
in the early embryonic brain and participate in neuronal circuit development.
Here, we find IBA1+ microglia-like cells alongside retinal cups between week 3
and 4 in 2.5D culture with an unguided retinal organoid differentiation protocol.
Microglia do not infiltrate the neuroectoderm and instead enrich within non-pigmented,
3D-cystic compartments that develop in parallel to the 3D-retinal organoids. When
we guide the retinal organoid differentiation with low-dosed BMP4, we prevent
cup development and enhance microglia and 3D-cysts formation. Mass spectrometry
identifies these 3D-cysts to express mesenchymal and epithelial markers. We confirmed
this microglia-preferred environment also within the unguided protocol, providing
insight into microglial behavior and migration and offer a model to study how
they enter and distribute within the human brain.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We thank the scientific service units at ISTA, specifically the lab
support facility and imaging & optics facility for their support; Nicolas Armel
for performing the Mass Spectrometry. We thank Alexandra Lang and Tanja Peilnsteiner
for their help in human brain tissue collection, Rouven Schulz for his insights
into the functional assays We thank all members of the Siegert group for constant
feedback on the project and Margaret Maes, Rouven Schulz, and Marco Benevento for
feedback on the manuscript. This project has received funding from the European
Research Council (ERC) under the European Union’s Horizon 2020 research and innovation
program (grant No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung
Niederösterreich (grant No. Sc19-017 to V.H.).
article_number: '104580'
article_processing_charge: Yes
article_type: original
author:
- first_name: Katarina
full_name: Bartalska, Katarina
id: 4D883232-F248-11E8-B48F-1D18A9856A87
last_name: Bartalska
- first_name: Verena
full_name: Hübschmann, Verena
id: 32B7C918-F248-11E8-B48F-1D18A9856A87
last_name: Hübschmann
- first_name: Medina
full_name: Korkut, Medina
id: 4B51CE74-F248-11E8-B48F-1D18A9856A87
last_name: Korkut
orcid: 0000-0003-4309-2251
- first_name: Ryan J
full_name: Cubero, Ryan J
id: 850B2E12-9CD4-11E9-837F-E719E6697425
last_name: Cubero
orcid: 0000-0003-0002-1867
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Karl
full_name: Rössler, Karl
last_name: Rössler
- first_name: Thomas
full_name: Czech, Thomas
last_name: Czech
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Bartalska K, Hübschmann V, Korkut M, et al. A systematic characterization of
microglia-like cell occurrence during retinal organoid differentiation. iScience.
2022;25(7). doi:10.1016/j.isci.2022.104580
apa: Bartalska, K., Hübschmann, V., Korkut, M., Cubero, R. J., Venturino, A., Rössler,
K., … Siegert, S. (2022). A systematic characterization of microglia-like cell
occurrence during retinal organoid differentiation. IScience. Elsevier.
https://doi.org/10.1016/j.isci.2022.104580
chicago: Bartalska, Katarina, Verena Hübschmann, Medina Korkut, Ryan J Cubero, Alessandro
Venturino, Karl Rössler, Thomas Czech, and Sandra Siegert. “A Systematic Characterization
of Microglia-like Cell Occurrence during Retinal Organoid Differentiation.” IScience.
Elsevier, 2022. https://doi.org/10.1016/j.isci.2022.104580.
ieee: K. Bartalska et al., “A systematic characterization of microglia-like
cell occurrence during retinal organoid differentiation,” iScience, vol.
25, no. 7. Elsevier, 2022.
ista: Bartalska K, Hübschmann V, Korkut M, Cubero RJ, Venturino A, Rössler K, Czech
T, Siegert S. 2022. A systematic characterization of microglia-like cell occurrence
during retinal organoid differentiation. iScience. 25(7), 104580.
mla: Bartalska, Katarina, et al. “A Systematic Characterization of Microglia-like
Cell Occurrence during Retinal Organoid Differentiation.” IScience, vol.
25, no. 7, 104580, Elsevier, 2022, doi:10.1016/j.isci.2022.104580.
short: K. Bartalska, V. Hübschmann, M. Korkut, R.J. Cubero, A. Venturino, K. Rössler,
T. Czech, S. Siegert, IScience 25 (2022).
date_created: 2022-07-03T22:01:33Z
date_published: 2022-07-15T00:00:00Z
date_updated: 2023-11-02T12:21:33Z
day: '15'
ddc:
- '610'
department:
- _id: SaSi
doi: 10.1016/j.isci.2022.104580
ec_funded: 1
external_id:
isi:
- '000830428500005'
file:
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checksum: a470b74e1b3796c710189c81a4cd4329
content_type: application/pdf
creator: cchlebak
date_created: 2022-07-04T08:19:25Z
date_updated: 2022-07-04T08:19:25Z
file_id: '11480'
file_name: 2022_iScience_Bartalska.pdf
file_size: 19400048
relation: main_file
success: 1
file_date_updated: 2022-07-04T08:19:25Z
has_accepted_license: '1'
intvolume: ' 25'
isi: 1
issue: '7'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '07'
oa: 1
oa_version: Published Version
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
- _id: B67AFEDC-15C9-11EA-A837-991A96BB2854
name: IST Austria Open Access Fund
- _id: 9B99D380-BA93-11EA-9121-9846C619BF3A
grant_number: SC19-017
name: How human microglia shape developing neurons during health and inflammation
publication: iScience
publication_identifier:
eissn:
- 2589-0042
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
- id: '12117'
relation: other
status: public
scopus_import: '1'
status: public
title: A systematic characterization of microglia-like cell occurrence during retinal
organoid differentiation
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: 25
year: '2022'
...
---
_id: '6412'
abstract:
- lang: eng
text: Polycomb group (PcG) proteins play critical roles in the epigenetic inheritance
of cell fate. The Polycomb Repressive Complexes PRC1 and PRC2 catalyse distinct
chromatin modifications to enforce gene silencing, but how transcriptional repression
is propagated through mitotic cell divisions remains a key unresolved question.
Using reversible tethering of PcG proteins to ectopic sites in mouse embryonic
stem cells, here we show that PRC1 can trigger transcriptional repression and
Polycomb-dependent chromatin modifications. We find that canonical PRC1 (cPRC1),
but not variant PRC1, maintains gene silencing through cell division upon reversal
of tethering. Propagation of gene repression is sustained by cis-acting histone
modifications, PRC2-mediated H3K27me3 and cPRC1-mediated H2AK119ub1, promoting
a sequence-independent feedback mechanism for PcG protein recruitment. Thus, the
distinct PRC1 complexes present in vertebrates can differentially regulate epigenetic
maintenance of gene silencing, potentially enabling dynamic heritable responses
to complex stimuli. Our findings reveal how PcG repression is potentially inherited
in vertebrates.
article_number: '1931'
article_processing_charge: No
author:
- first_name: Hagar F.
full_name: Moussa, Hagar F.
last_name: Moussa
- first_name: Daniel
full_name: Bsteh, Daniel
last_name: Bsteh
- first_name: Ramesh
full_name: Yelagandula, Ramesh
last_name: Yelagandula
- first_name: Carina
full_name: Pribitzer, Carina
last_name: Pribitzer
- first_name: Karin
full_name: Stecher, Karin
last_name: Stecher
- first_name: Katarina
full_name: Bartalska, Katarina
id: 4D883232-F248-11E8-B48F-1D18A9856A87
last_name: Bartalska
- first_name: Luca
full_name: Michetti, Luca
last_name: Michetti
- first_name: Jingkui
full_name: Wang, Jingkui
last_name: Wang
- first_name: Jorge A.
full_name: Zepeda-Martinez, Jorge A.
last_name: Zepeda-Martinez
- first_name: Ulrich
full_name: Elling, Ulrich
last_name: Elling
- first_name: Jacob I.
full_name: Stuckey, Jacob I.
last_name: Stuckey
- first_name: Lindsey I.
full_name: James, Lindsey I.
last_name: James
- first_name: Stephen V.
full_name: Frye, Stephen V.
last_name: Frye
- first_name: Oliver
full_name: Bell, Oliver
last_name: Bell
citation:
ama: Moussa HF, Bsteh D, Yelagandula R, et al. Canonical PRC1 controls sequence-independent
propagation of Polycomb-mediated gene silencing. Nature Communications.
2019;10(1). doi:10.1038/s41467-019-09628-6
apa: Moussa, H. F., Bsteh, D., Yelagandula, R., Pribitzer, C., Stecher, K., Bartalska,
K., … Bell, O. (2019). Canonical PRC1 controls sequence-independent propagation
of Polycomb-mediated gene silencing. Nature Communications. Springer Nature.
https://doi.org/10.1038/s41467-019-09628-6
chicago: Moussa, Hagar F., Daniel Bsteh, Ramesh Yelagandula, Carina Pribitzer, Karin
Stecher, Katarina Bartalska, Luca Michetti, et al. “Canonical PRC1 Controls Sequence-Independent
Propagation of Polycomb-Mediated Gene Silencing.” Nature Communications.
Springer Nature, 2019. https://doi.org/10.1038/s41467-019-09628-6.
ieee: H. F. Moussa et al., “Canonical PRC1 controls sequence-independent
propagation of Polycomb-mediated gene silencing,” Nature Communications,
vol. 10, no. 1. Springer Nature, 2019.
ista: Moussa HF, Bsteh D, Yelagandula R, Pribitzer C, Stecher K, Bartalska K, Michetti
L, Wang J, Zepeda-Martinez JA, Elling U, Stuckey JI, James LI, Frye SV, Bell O.
2019. Canonical PRC1 controls sequence-independent propagation of Polycomb-mediated
gene silencing. Nature Communications. 10(1), 1931.
mla: Moussa, Hagar F., et al. “Canonical PRC1 Controls Sequence-Independent Propagation
of Polycomb-Mediated Gene Silencing.” Nature Communications, vol. 10, no.
1, 1931, Springer Nature, 2019, doi:10.1038/s41467-019-09628-6.
short: H.F. Moussa, D. Bsteh, R. Yelagandula, C. Pribitzer, K. Stecher, K. Bartalska,
L. Michetti, J. Wang, J.A. Zepeda-Martinez, U. Elling, J.I. Stuckey, L.I. James,
S.V. Frye, O. Bell, Nature Communications 10 (2019).
date_created: 2019-05-13T07:58:35Z
date_published: 2019-04-29T00:00:00Z
date_updated: 2023-08-25T10:31:56Z
day: '29'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1038/s41467-019-09628-6
external_id:
isi:
- '000466118700002'
file:
- access_level: open_access
checksum: 6550a328335396c856db4cbdda7d2994
content_type: application/pdf
creator: dernst
date_created: 2019-05-14T08:45:51Z
date_updated: 2020-07-14T12:47:29Z
file_id: '6448'
file_name: 2019_NatureComm_Moussa.pdf
file_size: 1223647
relation: main_file
file_date_updated: 2020-07-14T12:47:29Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
issue: '1'
language:
- iso: eng
month: '04'
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: Canonical PRC1 controls sequence-independent propagation of Polycomb-mediated
gene silencing
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: 10
year: '2019'
...