Specification of diverse cell types during early neurogenesis of the mouse cerebellum

Elife. 2019 Feb 8;8:e42388. doi: 10.7554/eLife.42388.

Abstract

We applied single-cell RNA sequencing to profile genome-wide gene expression in about 9400 individual cerebellar cells from the mouse embryo at embryonic day 13.5. Reiterative clustering identified the major cerebellar cell types and subpopulations of different lineages. Through pseudotemporal ordering to reconstruct developmental trajectories, we identified novel transcriptional programs controlling cell fate specification of populations arising from the ventricular zone and the rhombic lip, two distinct germinal zones of the embryonic cerebellum. Together, our data revealed cell-specific markers for studying the cerebellum, gene-expression cascades underlying cell fate specification, and a number of previously unknown subpopulations that may play an integral role in the formation and function of the cerebellum. Our findings will facilitate new discovery by providing insights into the molecular and cell type diversity in the developing cerebellum.

Keywords: Purkinje neurons; cell fate specification; cerebellar nuclei; developmental biology; mouse; neural progenitors; organizer; single-cell transcriptomics.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Lineage / genetics
  • Cerebellum / growth & development*
  • Cerebellum / metabolism
  • Embryo, Mammalian
  • Embryonic Development / genetics*
  • Gene Expression Regulation, Developmental / genetics
  • Mice
  • Neurogenesis / genetics*
  • Neurons / metabolism
  • Sequence Analysis, RNA / methods
  • Single-Cell Analysis / methods
  • Transcription Factors / genetics

Substances

  • Transcription Factors