染色质可及性分析揭示了人类视网膜发育和 hiPSC 衍生的视网膜类器官的调控动态。

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

机构信息

Eye Center, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.

Neurodegenerative Disorder Research Center, CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei 230026, China.

出版信息

Sci Adv. 2020 Feb 7;6(6):eaay5247. doi: 10.1126/sciadv.aay5247. eCollection 2020 Feb.

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.

视网膜类器官（RO）来源于人诱导多能干细胞（hiPSC），为研究人类视网膜发育和疾病提供了潜在的机会；然而，RO 在多大程度上重现了人类视网膜发育的表观遗传特征尚不清楚。在这项研究中，我们系统地分析了长期的人类视网膜和 RO 发育过程中的染色质可及性和转录动力学。我们的结果表明，RO 在很大程度上重现了人类视网膜发生，但也发现了不同的染色质特征。我们进一步重建了体内调控人和 RO 视网膜发生的转录调控网络。值得注意的是，NFIB 和 THRA 被鉴定为人类视网膜发育的调控因子。还对发育中的人和鼠视网膜之间的染色质修饰进行了交叉分析。值得注意的是，我们在人类视网膜发生中发现了富含 H3K4me3 和 H3K27me3 的二价修饰，而在鼠类视网膜发生中则没有，这表明人类基因组有更专门的表观遗传调控。