Dermal Adipocyte Lipolysis and Myofibroblast Conversion Are Required for Efficient Skin Repair

Brett A Shook; Renee R Wasko; Omer Mano; Michael Rutenberg-Schoenberg; Michael C Rudolph; Bahar Zirak; Guillermo C Rivera-Gonzalez; Francesc López-Giráldez; Simona Zarini; Amélie Rezza; Damon A Clark; Michael Rendl; Michael D Rosenblum; Mark B Gerstein; Valerie Horsley

doi:10.1016/j.stem.2020.03.013

Dermal Adipocyte Lipolysis and Myofibroblast Conversion Are Required for Efficient Skin Repair

Cell Stem Cell. 2020 Jun 4;26(6):880-895.e6. doi: 10.1016/j.stem.2020.03.013. Epub 2020 Apr 16.

Authors

Affiliations

¹ Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.
² Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA; Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06511, USA.
³ Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA.
⁴ Division of Endocrinology, Metabolism and Diabetes, University of Colorado, Denver Anschutz Medical Campus, CO 80045, USA.
⁵ Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA.
⁶ Yale Center for Genome Analysis, Yale School of Medicine, New Haven, CT 06510, USA.
⁷ Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06511, USA.
⁸ Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 11766, USA; Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 11766, USA.
⁹ Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA; Department of Dermatology, Yale University, New Haven, CT 06511, USA. Electronic address: valerie.horsley@yale.edu.

Abstract

Mature adipocytes store fatty acids and are a common component of tissue stroma. Adipocyte function in regulating bone marrow, skin, muscle, and mammary gland biology is emerging, but the role of adipocyte-derived lipids in tissue homeostasis and repair is poorly understood. Here, we identify an essential role for adipocyte lipolysis in regulating inflammation and repair after injury in skin. Genetic mouse studies revealed that dermal adipocytes are necessary to initiate inflammation after injury and promote subsequent repair. We find through histological, ultrastructural, lipidomic, and genetic experiments in mice that adipocytes adjacent to skin injury initiate lipid release necessary for macrophage inflammation. Tamoxifen-inducible genetic lineage tracing of mature adipocytes and single-cell RNA sequencing revealed that dermal adipocytes alter their fate and generate ECM-producing myofibroblasts within wounds. Thus, adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes.

Keywords: cellular plasticity; dermal adipose tissue; inflammation; lipolysis; myofibroblast; wound healing.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes
Animals
Lipolysis*
Macrophages
Mice
Myofibroblasts*
Skin

Abstract

Publication types

MeSH terms

Grants and funding