mTORC1 is essential for early steps during Schwann cell differentiation of amniotic fluid stem cells and regulates lipogenic gene expression

PLoS One. 2014 Sep 15;9(9):e107004. doi: 10.1371/journal.pone.0107004. eCollection 2014.

Abstract

Schwann cell development is hallmarked by the induction of a lipogenic profile. Here we used amniotic fluid stem (AFS) cells and focused on the mechanisms occurring during early steps of differentiation along the Schwann cell lineage. Therefore, we initiated Schwann cell differentiation in AFS cells and monitored as well as modulated the activity of the mechanistic target of rapamycin (mTOR) pathway, the major regulator of anabolic processes. Our results show that mTOR complex 1 (mTORC1) activity is essential for glial marker expression and expression of Sterol Regulatory Element-Binding Protein (SREBP) target genes. Moreover, SREBP target gene activation by statin treatment promoted lipogenic gene expression, induced mTORC1 activation and stimulated Schwann cell differentiation. To investigate mTORC1 downstream signaling we expressed a mutant S6K1, which subsequently induced the expression of the Schwann cell marker S100b, but did not affect lipogenic gene expression. This suggests that S6K1 dependent and independent pathways downstream of mTORC1 drive AFS cells to early Schwann cell differentiation and lipogenic gene expression. In conclusion our results propose that future strategies for peripheral nervous system regeneration will depend on ways to efficiently induce the mTORC1 pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amniotic Fluid / cytology
  • Animals
  • Cell Differentiation
  • Gene Expression Regulation
  • Humans
  • Lipogenesis / genetics
  • Mechanistic Target of Rapamycin Complex 1
  • Mice, Inbred C57BL
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Multiprotein Complexes / physiology*
  • Schwann Cells / cytology*
  • Schwann Cells / metabolism
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • TOR Serine-Threonine Kinases / physiology*

Substances

  • Multiprotein Complexes
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1