Enhanced Neuronal Regeneration in the CAST/Ei Mouse Strain Is Linked to Expression of Differentiation Markers after Injury

Cell Rep. 2017 Aug 1;20(5):1136-1147. doi: 10.1016/j.celrep.2017.07.010.

Abstract

Peripheral nerve regeneration after injury requires a broad program of transcriptional changes. We investigated the basis for the enhanced nerve regenerative capacity of the CAST/Ei mouse strain relative to C57BL/6 mice. RNA sequencing of dorsal root ganglia (DRG) showed a CAST/Ei-specific upregulation of Ascl1 after injury. Ascl1 overexpression in DRG neurons of C57BL/6 mice enhanced their neurite outgrowth. Ascl1 is regulated by miR-7048-3p, which is downregulated in CAST/Ei mice. Inhibition of miR-7048-3p enhances neurite outgrowth. Following injury, CAST/Ei neurons largely retained their mature neuronal profile as determined by single-cell RNA- seq, whereas the C57BL/6 neurons acquired an immature profile. These findings suggest that one facet of the enhanced regenerative phenotype is preservation of neuronal identity in response to injury.

Keywords: Ascl1; CAST/Ei; RNA sequencing; dorsal root ganglia; miR-7048; regeneration; single-cell analyses.

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*
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Nerve Regeneration*
  • Neurites / metabolism*
  • Neurites / pathology
  • Peripheral Nerve Injuries / genetics
  • Peripheral Nerve Injuries / metabolism*
  • Peripheral Nerve Injuries / pathology

Substances

  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • MicroRNAs