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 Clark

Research output: Contribution to journalArticlepeer-review

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 over retinal organoid and in vivo retinal development, across 20 timepoints. Using both pseudotemporal and cross-species analyses, we examined the conservation of gene expression across retinal progenitor maturation and specification of all seven major retinal cell types. Furthermore, we examined gene expression differences between developing macula and periphery and between two distinct populations of horizontal cells. We also identify both shared and species-specific patterns of gene expression during human and mouse retinal development. Finally, we identify 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.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Oct 2 2019

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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