Distinct roles of NFATc1 and NFATc4 in human primary myoblast differentiation and in the maintenance of reserve cells

J Cell Sci. 2017 Sep 15;130(18):3083-3093. doi: 10.1242/jcs.198978. Epub 2017 Jul 31.

Abstract

Ca2+ signaling plays a key role during human myoblast differentiation. Among Ca2+-sensitive pathways, calcineurin is essential for myoblast differentiation and muscle regeneration. Nuclear factor of activated T-cell (NFAT) transcription factors are the major calcineurin targets. We investigated the expression and the role of each NFAT gene during human primary myoblast differentiation. We found that three NFAT isoforms are present, NFATc1, NFATc3 and NFATc4. Importantly, while their mRNA expression increases during differentiation, NFATc1 is more highly expressed in myotubes, whilst NFATc4 is specifically maintained in reserve cells. NFATc3 is present in both cell types, although no specific role during myoblast differentiation was observed. Knockdown of either NFATc1 or NFATc4 affects the differentiation process similarly, by decreasing the expression of late differentiation markers, but impairs myotube formation differently. Whereas NFATc1 knockdown strongly reduced the number and the surface area of myotubes, NFATc4 knockdown increased the surface area of myotubes and reduced the pool of reserve cells. We conclude that NFAT genes have specific roles in myotube formation and in the maintenance of the reserve cell pool during human postnatal myogenesis.

Keywords: Differentiation; Human; Myoblast; NFATc1; NFATc4; Reserve cells.

MeSH terms

  • Biomarkers / metabolism
  • Cell Differentiation* / genetics
  • Cell Survival
  • Cells, Cultured
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Humans
  • Myoblasts / cytology*
  • Myoblasts / metabolism*
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism*
  • PAX7 Transcription Factor / metabolism
  • Phenotype
  • RNA, Small Interfering / metabolism

Substances

  • Biomarkers
  • NFATC Transcription Factors
  • NFATC1 protein, human
  • NFATC4 protein, human
  • PAX7 Transcription Factor
  • RNA, Small Interfering