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Science. 2017 Feb 17;355(6326):748-752. doi: 10.1126/science.aai8792. Epub 2017 Jan 5.

Regeneration of fat cells from myofibroblasts during wound healing.

Author information

1
Department of Dermatology, Kligman Laboratories, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. plikus@uci.edu cotsarel@mail.med.upenn.edu.
2
Department of Developmental and Cell Biology, Sue and Bill Gross Stem Cell Research Center, Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA.
3
The Ronald O. Perelman Department of Dermatology, Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
4
The Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
5
Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
6
Department of Dermatology, Kligman Laboratories, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
7
Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
8
INSERM U967, Commissariat à L'énergie Atomique et aux Énergies Alternatives, Institut de Radiobiologie Cellulaire et Moléculaire 92265 Fontenay-aux-Roses Cedex, France.
9
Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Korea.
10
Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 328116, USA.
11
Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany.
12
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR7104, INSERM U964, Université de Strasbourg, Illkirch 67404, France.
13
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR7104, INSERM U964, Institut d'Etudes Avancées de l'Université de Strasbourg, Collège de France, Illkirch 67404, France.
14
Center for Tissue Engineering, Department of Plastic Surgery, University of California, Irvine, Irvine, CA 92868, USA.
15
The Saban Research Institute of Children's Hospital Los Angeles and Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA.
16
Departments of Medicine and Cellular and Molecular Medicine, Moores Cancer Center and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
17
Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
18
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.

Abstract

Although regeneration through the reprogramming of one cell lineage to another occurs in fish and amphibians, it has not been observed in mammals. We discovered in the mouse that during wound healing, adipocytes regenerate from myofibroblasts, a cell type thought to be differentiated and nonadipogenic. Myofibroblast reprogramming required neogenic hair follicles, which triggered bone morphogenetic protein (BMP) signaling and then activation of adipocyte transcription factors expressed during development. Overexpression of the BMP antagonist Noggin in hair follicles or deletion of the BMP receptor in myofibroblasts prevented adipocyte formation. Adipocytes formed from human keloid fibroblasts either when treated with BMP or when placed with human hair follicles in vitro. Thus, we identify the myofibroblast as a plastic cell type that may be manipulated to treat scars in humans.

PMID:
28059714
PMCID:
PMC5464786
DOI:
10.1126/science.aai8792
[Indexed for MEDLINE]
Free PMC Article

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