Single cell RNA sequencing identifies early diversity of sensory neurons forming via bi-potential intermediates

Nat Commun. 2020 Aug 21;11(1):4175. doi: 10.1038/s41467-020-17929-4.

Abstract

Somatic sensation is defined by the existence of a diversity of primary sensory neurons with unique biological features and response profiles to external and internal stimuli. However, there is no coherent picture about how this diversity of cell states is transcriptionally generated. Here, we use deep single cell analysis to resolve fate splits and molecular biasing processes during sensory neurogenesis in mice. Our results identify a complex series of successive and specific transcriptional changes in post-mitotic neurons that delineate hierarchical regulatory states leading to the generation of the main sensory neuron classes. In addition, our analysis identifies previously undetected early gene modules expressed long before fate determination although being clearly associated with defined sensory subtypes. Overall, the early diversity of sensory neurons is generated through successive bi-potential intermediates in which synchronization of relevant gene modules and concurrent repression of competing fate programs precede cell fate stabilization and final commitment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Core Binding Factor Alpha 3 Subunit / genetics
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Regulatory Networks
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurogenesis / genetics*
  • Neurons / physiology
  • Sensory Receptor Cells / cytology*
  • Sensory Receptor Cells / physiology*
  • Sequence Analysis, RNA / methods*
  • Single-Cell Analysis / methods*
  • Stem Cells

Substances

  • Core Binding Factor Alpha 3 Subunit
  • Runx3 protein, mouse