Single-cell atlas of the transcriptome and chromatin accessibility in the human retina

Jin Li; Jun Wang; Ignacio L. Ibarra; Xuesen Cheng; Malte D. Luecken; Jiaxiong Lu; Aboozar Monavarfeshani; Wenjun Yan; Yiqiao Zheng; Zhen Zuo; Samantha Lynn Zayas Colborn; Berenice Sarahi Cortez; Leah A. Owen; Brittney Wick; Xuan Bao; Maximilian Haeussler; Nicholas M. Tran; Karthik Shekhar; Joshua R. Sanes; J. Timothy Stout; Shiming Chen; Yumei Li; Margaret M. DeAngelis; Fabian J. Theis; Rui Chen

doi:10.1038/s41588-025-02454-1

Single-cell atlas of the transcriptome and chromatin accessibility in the human retina

Jin Li
, Jun Wang
, Ignacio L. Ibarra
, Xuesen Cheng
, Malte D. Luecken
, Jiaxiong Lu
, Aboozar Monavarfeshani
, Wenjun Yan
, Yiqiao Zheng
, Zhen Zuo
, Samantha Lynn Zayas Colborn
, Berenice Sarahi Cortez
, Leah A. Owen
, Brittney Wick
, Xuan Bao
, Maximilian Haeussler
, Nicholas M. Tran
, Karthik Shekhar
, Joshua R. Sanes
, J. Timothy Stout

Shiming Chen, Yumei Li, Margaret M. DeAngelis, Fabian J. Theis, Rui Chen

Department of Ophthalmology

University of California at Irvine
Baylor College of Medicine
Helmholtz Zentrum München - German Research Center for Environmental Health
German Center for Lung Research (DZL)
Harvard University
Washington University St. Louis
University of Utah
University of California at Santa Cruz
University of California at Berkeley

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Single-cell sequencing has revolutionized the scale and resolution of molecular profiling of tissues and organs. Here we present an integrated dual-modal reference atlas of the most accessible portion of the mammalian central nervous system, the retina. We compiled around 3.9 million cells from 125 donors of diverse ancestral backgrounds, including 8 published studies and 2.7 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) with more than 130 cell types identified. We annotated each cluster, identified marker genes and characterized cis-regulatory elements and gene regulatory networks. Our analysis uncovered differences in transcriptome, chromatin and gene regulatory networks across cell types. We modeled changes in gene expression and chromatin accessibility across age, ancestry and tissue region. This integrated atlas enhanced the fine-mapping of genome-wide association study and expression quantitative trait loci variants. Accessible through interactive browsers, this multimodal multidonor and multilab HRCA can facilitate a better understanding of retinal function and pathology.

Original language	English
Pages (from-to)	418-433
Number of pages	16
Journal	Nature Genetics
Volume	58
Issue number	2
DOIs	https://doi.org/10.1038/s41588-025-02454-1
State	Published - Feb 2026

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Li, J., Wang, J., Ibarra, I. L., Cheng, X., Luecken, M. D., Lu, J., Monavarfeshani, A., Yan, W., Zheng, Y., Zuo, Z., Colborn, S. L. Z., Cortez, B. S., Owen, L. A., Wick, B., Bao, X., Haeussler, M., Tran, N. M., Shekhar, K., Sanes, J. R., ... Chen, R. (2026). Single-cell atlas of the transcriptome and chromatin accessibility in the human retina. Nature Genetics, 58(2), 418-433. https://doi.org/10.1038/s41588-025-02454-1

@article{3fde3e6e8e2a4f2a8f7f07b87e23d981,

title = "Single-cell atlas of the transcriptome and chromatin accessibility in the human retina",

abstract = "Single-cell sequencing has revolutionized the scale and resolution of molecular profiling of tissues and organs. Here we present an integrated dual-modal reference atlas of the most accessible portion of the mammalian central nervous system, the retina. We compiled around 3.9 million cells from 125 donors of diverse ancestral backgrounds, including 8 published studies and 2.7 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) with more than 130 cell types identified. We annotated each cluster, identified marker genes and characterized cis-regulatory elements and gene regulatory networks. Our analysis uncovered differences in transcriptome, chromatin and gene regulatory networks across cell types. We modeled changes in gene expression and chromatin accessibility across age, ancestry and tissue region. This integrated atlas enhanced the fine-mapping of genome-wide association study and expression quantitative trait loci variants. Accessible through interactive browsers, this multimodal multidonor and multilab HRCA can facilitate a better understanding of retinal function and pathology.",

author = "Jin Li and Jun Wang and Ibarra, \{Ignacio L.\} and Xuesen Cheng and Luecken, \{Malte D.\} and Jiaxiong Lu and Aboozar Monavarfeshani and Wenjun Yan and Yiqiao Zheng and Zhen Zuo and Colborn, \{Samantha Lynn Zayas\} and Cortez, \{Berenice Sarahi\} and Owen, \{Leah A.\} and Brittney Wick and Xuan Bao and Maximilian Haeussler and Tran, \{Nicholas M.\} and Karthik Shekhar and Sanes, \{Joshua R.\} and Stout, \{J. Timothy\} and Shiming Chen and Yumei Li and DeAngelis, \{Margaret M.\} and Theis, \{Fabian J.\} and Rui Chen",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature America, Inc. 2026.",

year = "2026",

month = feb,

doi = "10.1038/s41588-025-02454-1",

language = "English",

volume = "58",

pages = "418--433",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

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Li, J, Wang, J, Ibarra, IL, Cheng, X, Luecken, MD, Lu, J, Monavarfeshani, A, Yan, W, Zheng, Y, Zuo, Z, Colborn, SLZ, Cortez, BS, Owen, LA, Wick, B, Bao, X, Haeussler, M, Tran, NM, Shekhar, K, Sanes, JR, Stout, JT, Chen, S, Li, Y, DeAngelis, MM, Theis, FJ & Chen, R 2026, 'Single-cell atlas of the transcriptome and chromatin accessibility in the human retina', Nature Genetics, vol. 58, no. 2, pp. 418-433. https://doi.org/10.1038/s41588-025-02454-1

TY - JOUR

T1 - Single-cell atlas of the transcriptome and chromatin accessibility in the human retina

AU - Li, Jin

AU - Wang, Jun

AU - Ibarra, Ignacio L.

AU - Cheng, Xuesen

AU - Luecken, Malte D.

AU - Lu, Jiaxiong

AU - Monavarfeshani, Aboozar

AU - Yan, Wenjun

AU - Zheng, Yiqiao

AU - Zuo, Zhen

AU - Colborn, Samantha Lynn Zayas

AU - Cortez, Berenice Sarahi

AU - Owen, Leah A.

AU - Wick, Brittney

AU - Bao, Xuan

AU - Haeussler, Maximilian

AU - Tran, Nicholas M.

AU - Shekhar, Karthik

AU - Sanes, Joshua R.

AU - Stout, J. Timothy

AU - Chen, Shiming

AU - Li, Yumei

AU - DeAngelis, Margaret M.

AU - Theis, Fabian J.

AU - Chen, Rui

PY - 2026/2

Y1 - 2026/2

N2 - Single-cell sequencing has revolutionized the scale and resolution of molecular profiling of tissues and organs. Here we present an integrated dual-modal reference atlas of the most accessible portion of the mammalian central nervous system, the retina. We compiled around 3.9 million cells from 125 donors of diverse ancestral backgrounds, including 8 published studies and 2.7 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) with more than 130 cell types identified. We annotated each cluster, identified marker genes and characterized cis-regulatory elements and gene regulatory networks. Our analysis uncovered differences in transcriptome, chromatin and gene regulatory networks across cell types. We modeled changes in gene expression and chromatin accessibility across age, ancestry and tissue region. This integrated atlas enhanced the fine-mapping of genome-wide association study and expression quantitative trait loci variants. Accessible through interactive browsers, this multimodal multidonor and multilab HRCA can facilitate a better understanding of retinal function and pathology.

AB - Single-cell sequencing has revolutionized the scale and resolution of molecular profiling of tissues and organs. Here we present an integrated dual-modal reference atlas of the most accessible portion of the mammalian central nervous system, the retina. We compiled around 3.9 million cells from 125 donors of diverse ancestral backgrounds, including 8 published studies and 2.7 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) with more than 130 cell types identified. We annotated each cluster, identified marker genes and characterized cis-regulatory elements and gene regulatory networks. Our analysis uncovered differences in transcriptome, chromatin and gene regulatory networks across cell types. We modeled changes in gene expression and chromatin accessibility across age, ancestry and tissue region. This integrated atlas enhanced the fine-mapping of genome-wide association study and expression quantitative trait loci variants. Accessible through interactive browsers, this multimodal multidonor and multilab HRCA can facilitate a better understanding of retinal function and pathology.

UR - https://www.scopus.com/pages/publications/105028563816

U2 - 10.1038/s41588-025-02454-1

DO - 10.1038/s41588-025-02454-1

M3 - Article

C2 - 41578023

AN - SCOPUS:105028563816

SN - 1061-4036

VL - 58

SP - 418

EP - 433

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

Single-cell atlas of the transcriptome and chromatin accessibility in the human retina

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