Integrative Single‐Cell Transcriptomics and Epigenomics Mapping of the Fetal Retina Developmental Dynamics

Author:

Li Ruonan1234,Liu Jiangyi1234,Yi Ping5,Yang Xianli5,Chen Jun6,Zhao Chenyang1234,Liao Xingyun127,Wang Xiaotang1234,Xu Zongren12,Lu Huiping1234,Li Hongshun1234,Zhang Zhi1234,Liu Xianyang1234,Xiang Junjie1234,Hu Ke1234,Qi Hongbo68,Yu Jia910,Yang Peizeng1234,Hou Shengping123411ORCID

Affiliation:

1. The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 P. R. China

2. Chongqing Key Laboratory of Ophthalmology Chongqing 400016 P. R. China

3. Chongqing Eye Institute Chongqing 400016 P. R. China

4. Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases Chongqing 400016 P. R. China

5. Department of Obstetrics and Gynecology The Third Affiliated Hospital of Chongqing Medical University Chongqing 401120 P. R. China

6. Department of Obstetrics Women and Children's Hospital of Chongqing Medical University Chongqing 401147 P. R. China

7. Department of Medical Oncology Chongqing University Cancer Hospital Chongqing 400030 P. R. China

8. Chongqing Key Laboratory of Maternal and Fetal Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 P. R. China

9. State Key Laboratory of Medical Molecular Biology Department of Biochemistry and Molecular Biology Haihe Laboratory of Cell Ecosystem Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College Beijing 100005 P. R. China

10. The Key Laboratory of RNA and Hematopoietic Regulation Chinese Academy of Medical Sciences Beijing 100005 P. R. China

11. Beijing Institute of Ophthalmology Beijing Tongren Eye Center Beijing Tongren Hospital Capital Medical University Beijing Ophthalmology & Visual Sciences Key Laboratory Beijing 100730 P. R. China

Abstract

AbstractThe underlying mechanisms that determine gene expression and chromatin accessibility in retinogenesis are poorly understood. Herein, single‐cell RNA sequencing and single‐cell assay for transposase‐accessible chromatin sequencing are performed on human embryonic eye samples obtained 9–26 weeks after conception to explore the heterogeneity of retinal progenitor cells (RPCs) and neurogenic RPCs. The differentiation trajectory from RPCs to 7 major types of retinal cells are verified. Subsequently, diverse lineage‐determining transcription factors are identified and their gene regulatory networks are refined at the transcriptomic and epigenomic levels. Treatment of retinospheres, with the inhibitor of RE1 silencing transcription factor, X5050, induces more neurogenesis with the regular arrangement, and a decrease in Müller glial cells. The signatures of major retinal cells and their correlation with pathogenic genes associated with multiple ocular diseases, including uveitis and age‐related macular degeneration are also described. A framework for the integrated exploration of single‐cell developmental dynamics of the human primary retina is provided.

Publisher

Wiley

Subject

General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)

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