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Skin Adipocyte Stem Cell Self-Renewal Is Regulated by a PDGFA/AKT-Signaling Axis
Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA..
Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Molecular Cell Biology.
Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA..
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2016 (English)In: Cell Stem Cell, ISSN 1934-5909, E-ISSN 1875-9777, Vol. 19, no 6, 738-751 p.Article in journal (Refereed) Published
Abstract [en]

Tissue growth and maintenance requires stem cell populations that self-renew, proliferate, and differentiate. Maintenance of white adipose tissue (WAT) requires the proliferation and differentiation of adipocyte stem cells (ASCs) to form postmitotic, lipid-filled mature adipocytes. Here we use the dynamic adipogenic program that occurs during hair growth to uncover an unrecognized regulator of ASC self-renewal and proliferation, PDGFA, which activates AKT signaling to drive and maintain the adipogenic program in the skin. Pdgfa expression is reduced in aged ASCs and is required for ASC proliferation and maintenance in the dermis, but not in other WATs. Our molecular and genetic studies uncover PI3K/AKT2 as a direct PDGFA target that is activated in ASCs during WAT hyperplasia and is functionally required for dermal ASC proliferation. Our data therefore reveal active mechanisms that regulate ASC self-renewal in the skin and show that distinct regulatory mechanisms operate in different WAT depots.

Place, publisher, year, edition, pages
2016. Vol. 19, no 6, 738-751 p.
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-312048DOI: 10.1016/j.stem.2016.09.002ISI: 000389474900012PubMedID: 27746098OAI: oai:DiVA.org:uu-312048DiVA: diva2:1062355
Available from: 2017-01-05 Created: 2017-01-04 Last updated: 2017-01-05Bibliographically approved

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