| Accession | PRJCA001143 | ||||||||||||||||||||||||||||||||
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| Title | Chromatin accessibility analysis reveals regulatory dynamics of developing human fetal retina and retinal organoids | ||||||||||||||||||||||||||||||||
| Relevance | Model organism | ||||||||||||||||||||||||||||||||
| Data types |
Epigenomics
Transcriptome or Gene expression Raw sequence reads |
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| Organisms | Homo sapiens | ||||||||||||||||||||||||||||||||
| Description | Vision starts from human retina which is a laminated tissue composed of multiple types of neurons and glial cells, however, our current knowledges of human retinal development are mostly learned from rodent studies. The molecular mechanisms underlying human retinal development largely remain unknown. Retinal organoids (ROs) derived from human induced pluripotent stem cells (hiPSCs) provide unique platforms to model human retinal development and disorders, while the extent to which organoid systems recapitulate the human retinal development remains unknown. To address the two questions, we conducted ATAC-seq and RNA-seq to systematically analyze the transcriptional and chromatin accessibility dynamics during RO and human retinal development. Our results revealed that developing human retina exhibited a unique pattern of chromatin dynamics correlated with the retinal neurogenesis, and ROs recapitulated the process in a great extent, though divergent chromatin features were also discovered. Further analysis by integrating the chromatin accessibility and transcriptome profiles, we reconstructed the transcriptional regulatory network governing the retinal neurogenesis in vivo. Notably, transcription factors NIFB and THRA were found as new regulators necessary in human retinal development, which were further experimentally validated by gene manipulation in ROs. Taken together, our study offers a deeper insight into molecular dynamics during human retinal development, offers a framework for the evaluation the in vivo and in vitro molecular characteristics of human retina, and pave ways to improve the RO culture by the guide of nature human retinal development. | ||||||||||||||||||||||||||||||||
| Sample scope | Multiisolate | ||||||||||||||||||||||||||||||||
| Release date | 2020-02-27 | ||||||||||||||||||||||||||||||||
| Publication |
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| Grants |
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| Submitter | qukun Lab (qukun@ustc.edu.cn) | ||||||||||||||||||||||||||||||||
| Organization | University of Science and Technology of China | ||||||||||||||||||||||||||||||||
| Submission date | 2018-11-28 |