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

Rivera-Gonzalez, Guillermo C. (author)
Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
Shook, Brett A. (author)
Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
Andrae, Johanna (author)
Uppsala universitet,Vaskulärbiologi
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Holtrup, Brandon (author)
Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
Bollag, Katherine (author)
Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
Betsholtz, Christer (author)
Karolinska Institutet,Uppsala universitet,Vaskulärbiologi
Rodeheffer, Matthew S. (author)
Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.;Yale Univ, Sect Comparat Med, New Haven, CT 06520 USA.
Horsley, Valerie (author)
Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.;Yale Univ, Dept Dermatol, Yale Sch Med, New Haven, CT 06520 USA.
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Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA Vaskulärbiologi (creator_code:org_t)
Elsevier BV, 2016
2016
English.
In: Cell Stem Cell. - : Elsevier BV. - 1934-5909 .- 1875-9777. ; 19:6, s. 738-751
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

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