Language

English

Publication Date

2-1-2026

Journal

Nature Genetics

DOI

10.1038/s41588-025-02454-1

PMID

41578023

PMCID

PMC13050529

PubMedCentral® Posted Date

4-6-2026

PubMedCentral® Full Text Version

Author MSS

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3.9 million cells from 125 donors of diverse ancestral backgrounds, including 8 published studies and 2.7 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) with more than 130 cell types identified.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.

Keywords

Humans, Retina, Chromatin, Transcriptome, Single-Cell Analysis, Genome-Wide Association Study, Single-Cell Gene Expression Analysis, Quantitative Trait Loci, Gene Regulatory Networks, Gene Expression Profiling

Published Open-Access

yes

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