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Cell Stem Cell. 2016 Dec 1;19(6):738-751. doi: 10.1016/j.stem.2016.09.002. Epub 2016 Oct 13.

Skin Adipocyte Stem Cell Self-Renewal Is Regulated by a PDGFA/AKT-Signaling Axis.

Author information

1
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
2
Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, Sweden.
3
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA; Section of Comparative Medicine, Yale University, New Haven, CT 06520, USA.
4
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA; Department of Dermatology, Yale School of Medicine, Yale University, New Haven, CT 06520, USA. Electronic address: valerie.horsley@yale.edu.

Abstract

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.

KEYWORDS:

PI3K/Akt signaling; Pdgfa; adipocyte stem cells; self-renewal; skin

PMID:
27746098
PMCID:
PMC5135565
[Available on 2017-12-01]
DOI:
10.1016/j.stem.2016.09.002
[Indexed for MEDLINE]
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