1. Chromatin accessibility analysis reveals regulatory dynamics of developing human retina and hiPSC-derived retinal organoids
- Author
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Xin Fang, Xiao Sun, Wen Zhang, Kai Dong, Haohuan Xie, Wenyang Yi, Ziqin Yao, Young Li, Yong Shen, Qiang Liu, Zu-Qi Zuo, Jin Bao, Tasneem Akhtar, Xiaoqun Wang, Suijuan Zhong, Mei Zhang, Min Wei, Tian Xue, Kun Qu, Qian Wu, and Huan Zhao
- Subjects
Organogenesis ,Induced Pluripotent Stem Cells ,Gene regulatory network ,Biology ,Retina ,Epigenesis, Genetic ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Animals ,Humans ,Gene Regulatory Networks ,Epigenetics ,Research Articles ,030304 developmental biology ,Regulation of gene expression ,0303 health sciences ,Multidisciplinary ,Gene Expression Profiling ,SciAdv r-articles ,Cell Differentiation ,Human Genetics ,Retinal ,Chromatin Assembly and Disassembly ,Immunohistochemistry ,eye diseases ,Chromatin ,Cell biology ,Organoids ,medicine.anatomical_structure ,Gene Expression Regulation ,chemistry ,H3K4me3 ,Human genome ,sense organs ,Biomarkers ,030217 neurology & neurosurgery ,Signal Transduction ,Research Article ,Developmental Biology - Abstract
Epigenetic and transcriptomic profiling of developing human retina and retinal organoids revealed regulators in human retinal development., 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.
- Published
- 2020