Polycomb repression complex 2 is required for the maintenance of retinal progenitor cells and balanced retinal differentiation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F18%3A00486285" target="_blank" >RIV/68378050:_____/18:00486285 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.ydbio.2017.11.004" target="_blank" >http://dx.doi.org/10.1016/j.ydbio.2017.11.004</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ydbio.2017.11.004" target="_blank" >10.1016/j.ydbio.2017.11.004</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Polycomb repression complex 2 is required for the maintenance of retinal progenitor cells and balanced retinal differentiation

Popis výsledku v původním jazyce

Polycomb repressive complexes maintain transcriptional repression of genes encoding crucial developmental regulators through chromatin modification. Here we investigated the role of Polycomb repressive complex 2 (PRC2) in retinal development by inactivating its key components Eed and Ezh2. Conditional deletion of Ezh2 resulted in a partial loss of PRC2 function and accelerated differentiation of Muller glial cells. In contrast, inactivation of Eed led to the ablation of PRC2 function at early postnatal stage. Cell proliferation was reduced and retinal progenitor cells were significantly decreased in this mutant, which subsequently caused depletion of Muller glia, bipolar, and rod photoreceptor cells, primarily generated from postnatal retinal progenitor cells. Interestingly, the proportion of amacrine cells was dramatically increased at postnatal stages in the Eed-deficient retina. In accordance, multiple transcription factors controlling amacrine cell differentiation were upregulated. Furthermore, ChIP-seq analysis showed that these deregulated genes contained bivalent chromatin (H3K27me3(+) H3K4me3(+)). Our results suggest that PRC2 is required for proliferation in order to maintain the retinal progenitor cells at postnatal stages and for retinal differentiation by controlling amacrine cell generation.

Název v anglickém jazyce

Polycomb repression complex 2 is required for the maintenance of retinal progenitor cells and balanced retinal differentiation

Popis výsledku anglicky

Polycomb repressive complexes maintain transcriptional repression of genes encoding crucial developmental regulators through chromatin modification. Here we investigated the role of Polycomb repressive complex 2 (PRC2) in retinal development by inactivating its key components Eed and Ezh2. Conditional deletion of Ezh2 resulted in a partial loss of PRC2 function and accelerated differentiation of Muller glial cells. In contrast, inactivation of Eed led to the ablation of PRC2 function at early postnatal stage. Cell proliferation was reduced and retinal progenitor cells were significantly decreased in this mutant, which subsequently caused depletion of Muller glia, bipolar, and rod photoreceptor cells, primarily generated from postnatal retinal progenitor cells. Interestingly, the proportion of amacrine cells was dramatically increased at postnatal stages in the Eed-deficient retina. In accordance, multiple transcription factors controlling amacrine cell differentiation were upregulated. Furthermore, ChIP-seq analysis showed that these deregulated genes contained bivalent chromatin (H3K27me3(+) H3K4me3(+)). Our results suggest that PRC2 is required for proliferation in order to maintain the retinal progenitor cells at postnatal stages and for retinal differentiation by controlling amacrine cell generation.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10602 - Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Developmental Biology

ISSN

0012-1606

e-ISSN

—

Svazek periodika

433

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

47-60

Kód UT WoS článku

000418394200005

EID výsledku v databázi Scopus

—