Chromatin accessibility analysis reveals regulatory dynamics of developing human retina and hiPSC-derived retinal organoids
Haohuan Xie, Wen Zhang, Mei Zhang, Tasneem Akhtar, Young Li, Wenyang Yi, Xiao Sun, Zuqi Zuo, Min Wei, Xin Fang, Ziqin Yao, Kai Dong, Suijuan Zhong, Qiang Liu, Yong Shen, Qian Wu, Xiaoqun Wang, Huan Zhao, Jin Bao, Kun Qu, and Tian Xue
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.
文章链接：https://advances.sciencemag.org/content/6/6/eaay5247
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