Comparative transcriptomic profiling reveals a role for Olig1 in promoting axon regeneration

Cell Rep. 2024 Jul 23;43(7):114514. doi: 10.1016/j.celrep.2024.114514. Epub 2024 Jul 13.

Abstract

The regenerative potential of injured axons displays considerable heterogeneity. However, the molecular mechanisms underlying the heterogeneity have not been fully elucidated. Here, we establish a method that can separate spinal motor neurons (spMNs) with low and high regenerative capacities and identify a set of transcripts revealing differential expression between two groups of neurons. Interestingly, oligodendrocyte transcription factor 1 (Olig1), which regulates the differentiation of various neuronal progenitors, exhibits recurrent expression in spMNs with enhanced regenerative capabilities. Furthermore, overexpression of Olig1 (Olig1 OE) facilitates axonal regeneration in various models, and down-regulation or deletion of Olig1 exhibits an opposite effect. By analyzing the overlapped differentially expressed genes after expressing individual Olig factor and functional validation, we find that the role of Olig1 is at least partially through the neurite extension factor 1 (Nrsn1). We therefore identify Olig1 as an intrinsic factor that promotes regenerative capacity of injured axons.

Keywords: CP: Genomics; CP: Neuroscience; Nrsn1; Olig1; axon regeneration.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Axons* / metabolism
  • Basic Helix-Loop-Helix Transcription Factors* / genetics
  • Basic Helix-Loop-Helix Transcription Factors* / metabolism
  • Gene Expression Profiling*
  • Mice
  • Mice, Inbred C57BL
  • Motor Neurons / metabolism
  • Nerve Regeneration* / genetics
  • Nerve Regeneration* / physiology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Transcriptome / genetics

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Olig1 protein, mouse
  • Nerve Tissue Proteins