Progenitor cell diversity in the developing mouse neocortex

Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):e2018866118. doi: 10.1073/pnas.2018866118.

Abstract

In the mammalian neocortex, projection neuron types are sequentially generated by the same pool of neural progenitors. How neuron type specification is related to developmental timing remains unclear. To determine whether temporal gene expression in neural progenitors correlates with neuron type specification, we performed single-cell RNA sequencing (scRNA-Seq) analysis of the developing mouse neocortex. We uncovered neuroepithelial cell enriched genes such as Hmga2 and Ccnd1 when compared to radial glial cells (RGCs). RGCs display dynamic gene expression over time; for instance, early RGCs express higher levels of Hes5, and late RGCs show higher expression of Pou3f2 Interestingly, intermediate progenitor cell marker gene Eomes coexpresses temporally with known neuronal identity genes at different developmental stages, though mostly in postmitotic cells. Our results delineate neural progenitor cell diversity in the developing mouse neocortex and support that neuronal identity genes are transcriptionally evident in Eomes-positive cells.

Keywords: cell identity; developmental timing; neural progenitor; neuronal diversity; scRNA-Seq.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation*
  • HMGA2 Protein / metabolism
  • Mice
  • Neocortex / cytology
  • Neocortex / embryology*
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • POU Domain Factors / metabolism
  • Repressor Proteins / metabolism
  • T-Box Domain Proteins / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Eomes protein, mouse
  • HMGA2 Protein
  • Hes5 protein, mouse
  • Nerve Tissue Proteins
  • POU Domain Factors
  • Repressor Proteins
  • T-Box Domain Proteins
  • Pou3f2 protein, mouse