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

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipocytes / cytology*
  • Adipocytes / enzymology*
  • Adipogenesis
  • Animals
  • CD24 Antigen / metabolism
  • Cell Proliferation
  • Cell Self Renewal*
  • Dermis / metabolism
  • Gene Expression Profiling
  • Hyperplasia
  • Mice, Inbred C57BL
  • Models, Biological
  • Phosphatidylinositol 3-Kinases / metabolism
  • Platelet-Derived Growth Factor / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Signal Transduction*
  • Skin / cytology*
  • Stem Cells / cytology*


  • CD24 Antigen
  • Platelet-Derived Growth Factor
  • platelet-derived growth factor A
  • Phosphatidylinositol 3-Kinases
  • Receptor, Platelet-Derived Growth Factor alpha
  • Proto-Oncogene Proteins c-akt