Single-Cell Analysis of Human Retina Identifies Evolutionarily Conserved and Species-Specific Mechanisms Controlling Development

Yufeng Lu, Fion Shiau, Wenyang Yi, Suying Lu, Qian Wu, Joel D. Pearson, Alyssa Kallman, Suijuan Zhong, Thanh Hoang, Zhentao Zuo, Fangqi Zhao, Mei Zhang, Nicole Tsai, Yan Zhuo, Sheng He, Jun Zhang, Genevieve L. Stein-O'Brien, Thomas D. Sherman, Xin Duan, Elana J. FertigLoyal A. Goff, Donald J. Zack, James T. Handa, Tian Xue, Rod Bremner, Seth Blackshaw, Xiaoqun Wang, Brian S. Clark

Research output: Contribution to journalArticle

Abstract

The development of single-cell RNA sequencing (scRNA-seq) has allowed high-resolution analysis of cell-type diversity and transcriptional networks controlling cell-fate specification. To identify the transcriptional networks governing human retinal development, we performed scRNA-seq analysis on 16 time points from developing retina as well as four early stages of retinal organoid differentiation. We identified evolutionarily conserved patterns of gene expression during retinal progenitor maturation and specification of all seven major retinal cell types. Furthermore, we identified gene-expression differences between developing macula and periphery and between distinct populations of horizontal cells. We also identified species-specific patterns of gene expression during human and mouse retinal development. Finally, we identified an unexpected role for ATOH7 expression in regulation of photoreceptor specification during late retinogenesis. These results provide a roadmap to future studies of human retinal development and may help guide the design of cell-based therapies for treating retinal dystrophies. Lu et al. performed scRNA-seq on the developing human retina and retinal organoids. Using comprehensive analyses, they deduced mechanisms regulating human retinal cell-fate specification and foveagenesis and contrasted these with murine retinal development. The data are a valuable resource for understanding human retinal development and disease.

Original languageEnglish (US)
Pages (from-to)473-491.e9
JournalDevelopmental Cell
Volume53
Issue number4
DOIs
StatePublished - May 18 2020

Keywords

  • cell fate
  • fovea
  • gene regulatory networks
  • neurogenesis
  • neurogenic bHLH factor
  • organoid
  • patterning
  • retina
  • single cell RNA-seq
  • transcription factors

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Lu, Y., Shiau, F., Yi, W., Lu, S., Wu, Q., Pearson, J. D., Kallman, A., Zhong, S., Hoang, T., Zuo, Z., Zhao, F., Zhang, M., Tsai, N., Zhuo, Y., He, S., Zhang, J., Stein-O'Brien, G. L., Sherman, T. D., Duan, X., ... Clark, B. S. (2020). Single-Cell Analysis of Human Retina Identifies Evolutionarily Conserved and Species-Specific Mechanisms Controlling Development. Developmental Cell, 53(4), 473-491.e9. https://doi.org/10.1016/j.devcel.2020.04.009