SOXF factors regulate murine satellite cell self-renewal and function through inhibition of β-catenin activity

Elife. 2018 Jun 8;7:e26039. doi: 10.7554/eLife.26039.

Abstract

Muscle satellite cells are the primary source of stem cells for postnatal skeletal muscle growth and regeneration. Understanding genetic control of satellite cell formation, maintenance, and acquisition of their stem cell properties is on-going, and we have identified SOXF (SOX7, SOX17, SOX18) transcriptional factors as being induced during satellite cell specification. We demonstrate that SOXF factors regulate satellite cell quiescence, self-renewal and differentiation. Moreover, ablation of Sox17 in the muscle lineage impairs postnatal muscle growth and regeneration. We further determine that activities of SOX7, SOX17 and SOX18 overlap during muscle regeneration, with SOXF transcriptional activity requisite. Finally, we show that SOXF factors also control satellite cell expansion and renewal by directly inhibiting the output of β-catenin activity, including inhibition of Ccnd1 and Axin2. Together, our findings identify a key regulatory function of SoxF genes in muscle stem cells via direct transcriptional control and interaction with canonical Wnt/β-catenin signaling.

Keywords: SoxF; adult stem cells; developmental biology; mouse; regenerative medicine; satellite cells; self-renewal; skeletal muscle regeneration; stem cells; ß-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axin Protein / metabolism
  • Cell Line
  • Cell Self Renewal*
  • Cyclin D1 / metabolism
  • HMGB Proteins / genetics
  • HMGB Proteins / metabolism*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • SOXF Transcription Factors / genetics
  • SOXF Transcription Factors / metabolism*
  • Satellite Cells, Skeletal Muscle / cytology
  • Satellite Cells, Skeletal Muscle / metabolism*
  • Wnt Signaling Pathway
  • beta Catenin / metabolism*

Substances

  • Axin Protein
  • Axin2 protein, mouse
  • Ccnd1 protein, mouse
  • HMGB Proteins
  • SOXF Transcription Factors
  • Sox17 protein, mouse
  • Sox18 protein, mouse
  • Sox7 protein, mouse
  • beta Catenin
  • Cyclin D1