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

0486285 - ÚMG 2018 RIV US eng J - Článek v odborném periodiku
Fujimura, Naoko - Kuželová, Andrea - Ebert, A. - Strnad, Hynek - Láchová, Jitka - Machoň, Ondřej - Busslinger, M. - Kozmik, Zbyněk
Polycomb repression complex 2 is required for the maintenance of retinal progenitor cells and balanced retinal differentiation.
Developmental Biology. Roč. 433, č. 1 (2018), s. 47-60. ISSN 0012-1606. E-ISSN 1095-564X
Grant CEP: GA ČR GA15-23675S; GA MŠMT(CZ) LQ1604; GA MŠMT(CZ) LM2015040; GA MŠMT ED2.1.00/19.0395
Institucionální podpora: RVO:68378050
Klíčová slova: Retina * Differentiation * Polycomb * Eed
Obor OECD: Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology
Impakt faktor: 2.936, rok: 2018

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.
Trvalý link: http://hdl.handle.net/11104/0281150