title: Amplification of Adipogenic Commitment by VSTM2A.
abstract: Despite progress in our comprehension of the mechanisms regulating adipose tissue development, the nature of the factors that functionally characterize adipose precursors is still elusive. Defining the early steps regulating adipocyte development is needed for the generation of tools to control adipose tissue size and function. Here, we report the discovery of V-set and transmembrane domain containing 2A (VSTM2A) as a protein expressed and secreted by committed preadipocytes. VSTM2A expression is elevated in the early phases of adipogenesis in vitro and adipose tissue development in vivo. We show that VSTM2A-producing cells associate with the vasculature and express the common surface markers of adipocyte progenitors. Overexpression of VSTM2A induces adipogenesis, whereas its depletion impairs this process. VSTM2A controls preadipocyte determination at least in part by modulating BMP signaling and PPARγ2 activation. We propose a model in which VSTM2A is produced to preserve and amplify the adipogenic capability of adipose precursors.
authors.affiliation: Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Université Laval, Faculté de médecine, 2725 Chemin Ste-Foy, QC G1V 4G5, Canada.
authors.forename: Blandine
authors.initials: B
authors.lastname: Secco
authors.affiliation: Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Université Laval, Faculté de médecine, 2725 Chemin Ste-Foy, QC G1V 4G5, Canada.
authors.forename: Étienne
authors.initials: É
authors.lastname: Camiré
authors.affiliation: Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Université Laval, Faculté de médecine, 2725 Chemin Ste-Foy, QC G1V 4G5, Canada.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Brière
authors.affiliation: Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Université Laval, Faculté de médecine, 2725 Chemin Ste-Foy, QC G1V 4G5, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Caron
authors.affiliation: Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Université Laval, Faculté de médecine, 2725 Chemin Ste-Foy, QC G1V 4G5, Canada.
authors.forename: Armande
authors.initials: A
authors.lastname: Billong
authors.affiliation: Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Université Laval, Faculté de médecine, 2725 Chemin Ste-Foy, QC G1V 4G5, Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: Gélinas
authors.affiliation: Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Université Laval, Faculté de médecine, 2725 Chemin Ste-Foy, QC G1V 4G5, Canada.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lemay
authors.affiliation: Program for Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Tharp
authors.affiliation: University of Massachusetts Medical School, Program in Molecular Medicine, Worcester, MA 01605, USA.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Lee
authors.affiliation: Centre hospitalier universitaire de Québec (CHU de Québec), Université Laval, Faculté de médecine, 2705 Boulevard Laurier, QC G1V 4G2, Canada.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gobeil
authors.affiliation: CIUSSS du Centre-Sud-de-l'ile-de-Montréal, CLSC des Faubourgs, 66 rue Sainte-Catherine Est, Montréal, QC H2X 1K6, Canada.
authors.forename: Jean V
authors.initials: JV
authors.lastname: Guimond
authors.affiliation: Centre Hospitalier Universitaire de Sainte-Justine (CHU de Sainte-Justine), Faculté de Médecine, Département de pathologie et biologie cellulaire, Université de Montréal, 3175 Chemin Côte Ste-Catherine, Montréal, QC H3T 1C5, Canada.
authors.forename: Natacha
authors.initials: N
authors.lastname: Patey
authors.affiliation: University of Massachusetts Medical School, Program in Molecular Medicine, Worcester, MA 01605, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Guertin
authors.affiliation: Program for Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stahl
authors.affiliation: Centre Hospitalier Universitaire de Sainte-Justine (CHU de Sainte-Justine), Faculté de Médecine, Département de pédiatrie et Département de microbiologie, infectiologie et immunologie, Université de Montréal, 3175 Chemin Côte Ste-Catherine, Montréal, QC H3T 1C5, Canada.
authors.forename: Élie
authors.initials: É
authors.lastname: Haddad
authors.affiliation: Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Université Laval, Faculté de médecine, 2725 Chemin Ste-Foy, QC G1V 4G5, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Marsolais
authors.affiliation: Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Université Laval, Faculté de médecine, 2725 Chemin Ste-Foy, QC G1V 4G5, Canada.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Bossé
authors.affiliation: Laboratory of Metabolic Regulation and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Kivanc
authors.initials: K
authors.lastname: Birsoy
authors.affiliation: Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Université Laval, Faculté de médecine, 2725 Chemin Ste-Foy, QC G1V 4G5, Canada. Electronic address: mathieu.laplante@criucpq.ulaval.ca.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Laplante
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis; D052436:Adipose Tissue, White / Q000098:blood supply / Q000166:cytology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D041681:NIH 3T3 Cells; D018919:Neovascularization, Physiologic; D047495:PPAR gamma / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D008565:Membrane Proteins; D047495:PPAR gamma; D011971:Receptors, Immunologic; C000624906:VSTM2 protein, mouse; C000624907:VSTM2A protein, human
keywords: 3T3-L1; adipogenesis; adipogenic commitment; adipose tissue; cell differentiation; cell signaling; obesity; preadipocyte