title: mTORC1 is essential for early steps during Schwann cell differentiation of amniotic fluid stem cells and regulates lipogenic gene expression.
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.
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Preitschopf
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Kongzhao
authors.initials: K
authors.lastname: Li
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.
authors.forename: David
authors.initials: D
authors.lastname: Schörghofer
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Kinslechner
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Schütz
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.
authors.forename: Ha
authors.initials: H
authors.lastname: Thi Thanh Pham
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.
authors.forename: Margit
authors.initials: M
authors.lastname: Rosner
authors.affiliation: 1st Department of Obstetrics and Gynaecology, Semmelweis University Medical School, Budapest, Hungary.
authors.forename: Gabor Jozsef
authors.initials: GJ
authors.lastname: Joo
authors.affiliation: Institute of Medical Chemistry, Medical University of Vienna, Vienna, Austria.
authors.forename: Clemens
authors.initials: C
authors.lastname: Röhrl
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Weichhart
authors.affiliation: Institute of Medical Chemistry, Medical University of Vienna, Vienna, Austria.
authors.forename: Herbert
authors.initials: H
authors.lastname: Stangl
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Hengstschläger
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.
authors.forename: Mario
authors.initials: M
authors.lastname: Mikula
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology; D000818:Animals; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D006801:Humans; D050155:Lipogenesis / Q000235:genetics; D000076222:Mechanistic Target of Rapamycin Complex 1; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012583:Schwann Cells / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D046912:Multiprotein Complexes; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases