Regulation of stem cell identity by miR-200a during spinal cord regeneration

Development. 2022 Feb 1;149(3):dev200033. doi: 10.1242/dev.200033. Epub 2022 Feb 14.

Abstract

Axolotls are an important model organism for multiple types of regeneration, including functional spinal cord regeneration. Remarkably, axolotls can repair their spinal cord after a small lesion injury and can also regenerate their entire tail following amputation. Several classical signaling pathways that are used during development are reactivated during regeneration, but how this is regulated remains a mystery. We have previously identified miR-200a as a key factor that promotes successful spinal cord regeneration. Here, using RNA-seq analysis, we discovered that the inhibition of miR-200a results in an upregulation of the classical mesodermal marker brachyury in spinal cord cells after injury. However, these cells still express the neural stem cell marker sox2. In vivo cell tracking allowed us to determine that these cells can give rise to cells of both the neural and mesoderm lineage. Additionally, we found that miR-200a can directly regulate brachyury via a seed sequence in the 3'UTR of the gene. Our data indicate that miR-200a represses mesodermal cell fate after a small lesion injury in the spinal cord when only glial cells and neurons need to be replaced.

Keywords: Axolotl; Mesoderm; Regeneration; Spinal cord; Stem cell.

Publication types

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

MeSH terms

  • 3' Untranslated Regions
  • Ambystoma mexicanum / metabolism
  • Animals
  • Antagomirs / metabolism
  • Cell Differentiation
  • Fetal Proteins / genetics
  • Fetal Proteins / metabolism
  • Mesoderm / cytology
  • Mesoderm / metabolism
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Spinal Cord / cytology
  • Spinal Cord / metabolism*
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / pathology
  • Spinal Cord Regeneration / genetics*
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • Tail / physiology
  • Wnt Signaling Pathway
  • beta Catenin / antagonists & inhibitors
  • beta Catenin / chemistry
  • beta Catenin / metabolism

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • Fetal Proteins
  • MicroRNAs
  • SOXB1 Transcription Factors
  • T-Box Domain Proteins
  • beta Catenin
  • Brachyury protein