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3.9 million cells from 125 donors of diverse ancestral backgrounds, including 8 published studies and 2.7 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) with more than 130 cell types identified.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

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

  • 期刊论文

  • 发表日期：

    2026年1月23日

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  • 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,
  • Jongsu Choi,
  • 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

摘要

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3.9 million cells from 125 donors of diverse ancestral backgrounds, including 8 published studies and 2.7 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) with more than 130 cell types identified.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