Multi-species single-cell transcriptomic analysis of ocular compartment regulons

被引:68
作者
Gautam, Pradeep [1 ,2 ]
Hamashima, Kiyofumi [1 ]
Chen, Ying [1 ,2 ,3 ]
Zeng, Yingying [1 ,4 ]
Makovoz, Bar [5 ]
Parikh, Bhav Harshad [6 ,7 ]
Lee, Hsin Yee [1 ]
Lau, Katherine Anne [1 ]
Su, Xinyi [6 ,7 ,8 ]
Wong, Raymond C. B. [9 ,10 ,11 ]
Chan, Woon-Khiong [2 ,3 ]
Li, Hu [12 ]
Blenkinsop, Timothy A. [5 ]
Loh, Yuin-Han [1 ,2 ,3 ,13 ]
机构
[1] A STAR Inst Mol & Cell Biol, Cell Fate Engn & Therapeut Lab, Singapore 138673, Singapore
[2] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore
[3] Natl Univ Singapore, NUS Grad Sch, Integrat Sci & Engn Programme ISEP, 21 Lower Kent Ridge Rd, Singapore 119077, Singapore
[4] Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore
[5] Icahn Sch Med Mt Sinai, New York, NY 10029 USA
[6] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore
[7] A STAR Inst Mol & Cell Biol, Translat Retinal Res Lab, Singapore 138673, Singapore
[8] Singapore Eye Res Inst, 11 Third Hosp Ave, Singapore 168751, Singapore
[9] Ctr Eye Res Australia, Melbourne, Vic, Australia
[10] Univ Melbourne, Dept Surg, Ophthalmol, Melbourne, Vic, Australia
[11] Shenzhen Univ, Shenzhen Eye Hosp, Sch Med, Shenzhen, Peoples R China
[12] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Ctr Individualized Med, Rochester, MN 55905 USA
[13] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117593, Singapore
关键词
RETINAL STEM-CELLS; EXPRESSION; DIFFERENTIATION; REGENERATION; FIBROBLASTS; ACTIVATION; PROGENITOR; PROTEIN; KLF7; EYE;
D O I
10.1038/s41467-021-25968-8
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A comprehensive analysis of the ocular networks among various tissues is necessary to understand eye physiology in health and disease. Here the authors present a multi-species single-cell transcriptomic atlas consisting of cells of the cornea, iris, ciliary body, neural retina, retinal pigmented epithelium, and choroid. The retina is a widely profiled tissue in multiple species by single-cell RNA sequencing studies. However, integrative research of the retina across species is lacking. Here, we construct the first single-cell atlas of the human and porcine ocular compartments and study inter-species differences in the retina. In addition to that, we identify putative adult stem cells present in the iris tissue. We also create a disease map of genes involved in eye disorders across compartments of the eye. Furthermore, we probe the regulons of different cell populations, which include transcription factors and receptor-ligand interactions and reveal unique directional signalling between ocular cell types. In addition, we study conservation of regulons across vertebrates and zebrafish to identify common core factors. Here, we show perturbation of KLF7 gene expression during retinal ganglion cells differentiation and conclude that it plays a significant role in the maturation of retinal ganglion cells.
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页数:14
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