Single-Cell RNA-Seq Analysis of Retinal Development Identifies NFI Factors as Regulating Mitotic Exit and Late-Born Cell Specification

Neuron. 2019 Jun 19;102(6):1111-1126.e5. doi: 10.1016/j.neuron.2019.04.010. Epub 2019 May 22.


Precise temporal control of gene expression in neuronal progenitors is necessary for correct regulation of neurogenesis and cell fate specification. However, the cellular heterogeneity of the developing CNS has posed a major obstacle to identifying the gene regulatory networks that control these processes. To address this, we used single-cell RNA sequencing to profile ten developmental stages encompassing the full course of retinal neurogenesis. This allowed us to comprehensively characterize changes in gene expression that occur during initiation of neurogenesis, changes in developmental competence, and specification and differentiation of each major retinal cell type. We identify the NFI transcription factors (Nfia, Nfib, and Nfix) as selectively expressed in late retinal progenitor cells and show that they control bipolar interneuron and Müller glia cell fate specification and promote proliferative quiescence.

Keywords: CoGAPS; Müller glia; cell fate; development; neural progenitor; neurogenesis; photoreceptor; proliferation; retina; scRNA-seq; single-cell RNA-sequencing.

Publication types

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

MeSH terms

  • Animals
  • Cell Proliferation / genetics
  • Ependymoglial Cells / metabolism
  • Gene Expression Regulation, Developmental / genetics*
  • Interneurons / metabolism
  • Mice
  • Mitosis / genetics
  • NFI Transcription Factors / genetics
  • Neural Stem Cells / metabolism*
  • Neurogenesis / genetics*
  • RNA-Seq
  • Retina / embryology*
  • Retina / growth & development
  • Retina / metabolism
  • Retinal Neurons / metabolism*
  • Single-Cell Analysis


  • NFI Transcription Factors
  • Nfia protein, mouse
  • Nfib protein, mouse
  • Nfix protein, mouse