Polycomb repression complex 2 is required for the maintenance of retinal progenitor cells and balanced retinal differentiation
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
29137925
DOI
10.1016/j.ydbio.2017.11.004
PII: S0012-1606(17)30327-5
Knihovny.cz E-zdroje
- Klíčová slova
- Differentiation, Eed, Polycomb, Retina,
- MeSH
- buněčná diferenciace fyziologie MeSH
- chromatin metabolismus MeSH
- EZH2 protein metabolismus MeSH
- histony metabolismus MeSH
- kmenové buňky cytologie metabolismus MeSH
- metylace MeSH
- myši MeSH
- neurogeneze MeSH
- neuroglie metabolismus MeSH
- PRC2 metabolismus MeSH
- proliferace buněk MeSH
- retina metabolismus fyziologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chromatin MeSH
- Eed protein, mouse MeSH Prohlížeč
- Ezh2 protein, mouse MeSH Prohlížeč
- EZH2 protein MeSH
- histony MeSH
- PRC2 MeSH
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 Müller 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 Müller 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.
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