Single cell transcriptomics reveals lineage trajectory of retinal ganglion cells in wild-type and Atoh7-null retinas

Nat Commun. 2021 Mar 5;12(1):1465. doi: 10.1038/s41467-021-21704-4.


Atoh7 has been believed to be essential for establishing the retinal ganglion cell (RGC) lineage, and Pou4f2 and Isl1 are known to regulate RGC specification and differentiation. Here we report our further study of the roles of these transcription factors. Using bulk RNA-seq, we identify genes regulated by the three transcription factors, which expand our understanding of the scope of downstream events. Using scRNA-seq on wild-type and mutant retinal cells, we reveal a transitional cell state of retinal progenitor cells (RPCs) co-marked by Atoh7 and other genes for different lineages and shared by all early retinal lineages. We further discover the unexpected emergence of the RGC lineage in the absence of Atoh7. We conclude that competence of RPCs for different retinal fates is defined by lineage-specific genes co-expressed in the transitional state and that Atoh7 defines the RGC competence and collaborates with other factors to shepherd transitional RPCs to the RGC lineage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • LIM-Homeodomain Proteins / genetics
  • LIM-Homeodomain Proteins / metabolism
  • Loss of Function Mutation
  • Mice
  • Nerve Tissue Proteins / metabolism*
  • RNA, Small Cytoplasmic
  • Retina / metabolism*
  • Retinal Ganglion Cells / metabolism*
  • Sequence Analysis
  • Stem Cells
  • Transcription Factor Brn-3B / genetics
  • Transcription Factor Brn-3B / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptome*


  • Atoh7 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Nerve Tissue Proteins
  • Pou4f2 protein, mouse
  • RNA, Small Cytoplasmic
  • Transcription Factor Brn-3B
  • Transcription Factors
  • insulin gene enhancer binding protein Isl-1