A multi-omics atlas of the human retina at single-cell resolution

Qingnan Liang; Xuesen Cheng; Jun Wang; Leah Owen; Akbar Shakoor; John L Lillvis; Charles Zhang; Michael Farkas; Ivana K Kim; Yumei Li; Margaret DeAngelis; Rui Chen

doi:10.1016/j.xgen.2023.100298

A multi-omics atlas of the human retina at single-cell resolution

Cell Genom. 2023 Apr 11;3(6):100298. doi: 10.1016/j.xgen.2023.100298. eCollection 2023 Jun 14.

Authors

Qingnan Liang^{1

2}, Xuesen Cheng¹, Jun Wang¹, Leah Owen^{3

4

5}, Akbar Shakoor⁵, John L Lillvis^{5

6}, Charles Zhang⁵, Michael Farkas^{5

6}, Ivana K Kim⁷, Yumei Li¹, Margaret DeAngelis^{3

4

5

6}, Rui Chen^{1

2}

Affiliations

¹ HGSC, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
² Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
³ Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT 84132, USA.
⁴ Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84132, USA.
⁵ Department of Ophthalmology, Jacobs School of Medicine and Biomedical Engineering, University at Buffalo SUNY, Buffalo, NY 14203, USA.
⁶ VA Western New York Healthcare System, Buffalo, NY 14215, USA.
⁷ Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA.

Abstract

Cell classes in the human retina are highly heterogeneous with their abundance varying by several orders of magnitude. Here, we generated and integrated a multi-omics single-cell atlas of the adult human retina, including more than 250,000 nuclei for single-nuclei RNA-seq and 137,000 nuclei for single-nuclei ATAC-seq. Cross-species comparison of the retina atlas among human, monkey, mice, and chicken revealed relatively conserved and non-conserved types. Interestingly, the overall cell heterogeneity in primate retina decreases compared with that of rodent and chicken retina. Through integrative analysis, we identified 35,000 distal cis-element-gene pairs, constructed transcription factor (TF)-target regulons for more than 200 TFs, and partitioned the TFs into distinct co-active modules. We also revealed the heterogeneity of the cis-element-gene relationships in different cell types, even from the same class. Taken together, we present a comprehensive single-cell multi-omics atlas of the human retina as a resource that enables systematic molecular characterization at individual cell-type resolution.

Keywords: cross-species analysis; gene regulation; human retina; single-cell multi-omics.

Grants and funding

K08 EY031800/EY/NEI NIH HHS/United States