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

Pradeep Gautam, Kiyofumi Hamashima, Ying Chen, Yingying Zeng, Bar Makovoz, Bhav Harshad Parikh, Hsin Yee Lee, Katherine Anne Lau, Xinyi Su, Raymond C. B. Wong, Woon-Khiong Chan, Hu Li (), Timothy A. Blenkinsop () and Yuin-Han Loh ()
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Pradeep Gautam: Cell Fate Engineering and Therapeutics Laboratory, A*STAR Institute of Molecular and Cell Biology
Kiyofumi Hamashima: Cell Fate Engineering and Therapeutics Laboratory, A*STAR Institute of Molecular and Cell Biology
Ying Chen: Cell Fate Engineering and Therapeutics Laboratory, A*STAR Institute of Molecular and Cell Biology
Yingying Zeng: Cell Fate Engineering and Therapeutics Laboratory, A*STAR Institute of Molecular and Cell Biology
Bar Makovoz: Icahn School of Medicine at Mount Sinai
Bhav Harshad Parikh: Yong Loo Lin School of Medicine, National University of Singapore
Hsin Yee Lee: Cell Fate Engineering and Therapeutics Laboratory, A*STAR Institute of Molecular and Cell Biology
Katherine Anne Lau: Cell Fate Engineering and Therapeutics Laboratory, A*STAR Institute of Molecular and Cell Biology
Xinyi Su: Yong Loo Lin School of Medicine, National University of Singapore
Raymond C. B. Wong: Centre for Eye Research Australia
Woon-Khiong Chan: National University of Singapore
Hu Li: Center for Individualized Medicine, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic
Timothy A. Blenkinsop: Icahn School of Medicine at Mount Sinai
Yuin-Han Loh: Cell Fate Engineering and Therapeutics Laboratory, A*STAR Institute of Molecular and Cell Biology

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-25968-8

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