title: Snail1 controls TGF-β responsiveness and differentiation of mesenchymal stem cells.
abstract: The Snail1 transcriptional repressor plays a key role in triggering epithelial-to-mesenchymal transition. Although Snail1 is widely expressed in early development, in adult animals it is limited to a subset of mesenchymal cells where it has a largely unknown function. Using a mouse model with inducible depletion of Snail1, here we demonstrate that Snail1 is required to maintain mesenchymal stem cells (MSCs). This effect is associated to the responsiveness to transforming growth factor (TGF)-β1 that shows a strong Snail1 dependence. Snail1 depletion in conditional knockout adult animals causes a significant decrease in the number of bone marrow-derived MSCs. In culture, Snail1-deficient MSCs prematurely differentiate to osteoblasts or adipocytes and, in contrast to controls, are resistant to the TGF-β1-induced differentiation block. These results demonstrate a new role for Snail1 in TGF-β response and MSC maintenance.
authors.affiliation: Programa de Recerca en Càncer, IMIM-Hospital del Mar, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Batlle
authors.forename: L
authors.initials: L
authors.lastname: Alba-Castellón
authors.forename: J
authors.initials: J
authors.lastname: Loubat-Casanovas
authors.forename: E
authors.initials: E
authors.lastname: Armenteros
authors.forename: C
authors.initials: C
authors.lastname: Francí
authors.forename: J
authors.initials: J
authors.lastname: Stanisavljevic
authors.forename: R
authors.initials: R
authors.lastname: Banderas
authors.forename: J
authors.initials: J
authors.lastname: Martin-Caballero
authors.forename: F
authors.initials: F
authors.lastname: Bonilla
authors.forename: J
authors.initials: J
authors.lastname: Baulida
authors.forename: J I
authors.initials: JI
authors.lastname: Casal
authors.forename: T
authors.initials: T
authors.lastname: Gridley
authors.forename: A
authors.initials: A
authors.lastname: García de Herreros
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D055786:Gene Knockout Techniques; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta