Chromatin accessibility analysis reveals regulatory dynamics of developing human retina and hiPSC-derived retinal organoids

Haohuan Xie(University of Science and Technology of China), Wen Zhang(University of Science and Technology of China), Mei Zhang(University of Science and Technology of China), Tasneem Akhtar(University of Science and Technology of China), Young Li(University of Science and Technology of China), Wenyang Yi(University of Science and Technology of China), Xiao Sun(University of Science and Technology of China), Zu-Qi Zuo(University of Science and Technology of China), Min Wei(University of Science and Technology of China), Xin Fang(University of Science and Technology of China), Ziqin Yao(University of Science and Technology of China), Kai Dong(University of Science and Technology of China), Suijuan Zhong(Chinese Academy of Sciences), Qiang Liu(University of Science and Technology of China), Yong Shen(University of Science and Technology of China), Qian Wu(Chinese Academy of Sciences), Xiaoqun Wang(Chinese Academy of Sciences), Huan Zhao(Hefei University), Jin Bao(University of Science and Technology of China), Kun Qu(University of Science and Technology of China), Tian Xue(University of Science and Technology of China)
Science Advances
February 7, 2020
10.1126/sciadv.aay5247
Cited by 77Open Access
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Abstract

Retinal organoids (ROs) derived from human induced pluripotent stem cells (hiPSCs) provide potential opportunities for studying human retinal development and disorders; however, to what extent ROs recapitulate the epigenetic features of human retinal development is unknown. In this study, we systematically profiled chromatin accessibility and transcriptional dynamics over long-term human retinal and RO development. Our results showed that ROs recapitulated the human retinogenesis to a great extent, but divergent chromatin features were also discovered. We further reconstructed the transcriptional regulatory network governing human and RO retinogenesis in vivo. Notably, NFIB and THRA were identified as regulators in human retinal development. The chromatin modifications between developing human and mouse retina were also cross-analyzed. Notably, we revealed an enriched bivalent modification of H3K4me3 and H3K27me3 in human but not in murine retinogenesis, suggesting a more dedicated epigenetic regulation on human genome.

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