title: Regeneration of fat cells from myofibroblasts during wound healing.
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.
authors.affiliation: 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.|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.
authors.forename: Maksim V
authors.identifier: 0000-0002-8845-2559
authors.initials: MV
authors.lastname: Plikus
authors.affiliation: 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.
authors.forename: Christian F
authors.identifier: 0000-0002-6245-6412
authors.initials: CF
authors.lastname: Guerrero-Juarez
authors.affiliation: The Ronald O. Perelman Department of Dermatology, Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ito
authors.affiliation: The Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Yun Rose
authors.identifier: 0000-0002-8077-4975
authors.initials: YR
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Priya H
authors.initials: PH
authors.lastname: Dedhia
authors.affiliation: Department of Dermatology, Kligman Laboratories, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ying
authors.identifier: 0000-0002-1906-9660
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Mengle
authors.identifier: 0000-0002-5488-9904
authors.initials: M
authors.lastname: Shao
authors.affiliation: Department of Dermatology, Kligman Laboratories, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.|INSERM U967, Commissariat à L'énergie Atomique et aux Énergies Alternatives, Institut de Radiobiologie Cellulaire et Moléculaire 92265 Fontenay-aux-Roses Cedex, France.
authors.forename: Denise L
authors.identifier: 0000-0001-7340-8427
authors.initials: DL
authors.lastname: Gay
authors.affiliation: 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.
authors.forename: Raul
authors.initials: R
authors.lastname: Ramos
authors.affiliation: 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.
authors.forename: Tsai-Ching
authors.initials: TC
authors.lastname: Hsi
authors.affiliation: 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.|Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Ji Won
authors.identifier: 0000-0001-5742-5120
authors.initials: JW
authors.lastname: Oh
authors.affiliation: 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.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Amanda
authors.identifier: 0000-0001-9584-7674
authors.initials: A
authors.lastname: Ramirez
authors.affiliation: 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.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Konopelski
authors.affiliation: 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.
authors.forename: Arijh
authors.identifier: 0000-0001-6122-6220
authors.initials: A
authors.lastname: Elzein
authors.affiliation: Department of Dermatology, Kligman Laboratories, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Anne
authors.identifier: 0000-0001-7064-7895
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Kligman Laboratories, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Rarinthip June
authors.initials: RJ
authors.lastname: Supapannachart
authors.affiliation: 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.
authors.forename: Hye-Lim
authors.initials: HL
authors.lastname: Lee
authors.affiliation: The Ronald O. Perelman Department of Dermatology, Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Chae Ho
authors.initials: CH
authors.lastname: Lim
authors.affiliation: Department of Dermatology, Kligman Laboratories, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Arben
authors.identifier: 0000-0003-1039-4042
authors.initials: A
authors.lastname: Nace
authors.affiliation: Department of Dermatology, Kligman Laboratories, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Amy
authors.identifier: 0000-0002-6298-4821
authors.initials: A
authors.lastname: Guo
authors.affiliation: Department of Dermatology, Kligman Laboratories, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Elsa
authors.initials: E
authors.lastname: Treffeisen
authors.affiliation: Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 328116, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Andl
authors.affiliation: 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.
authors.forename: Ricardo N
authors.identifier: 0000-0002-1259-5406
authors.initials: RN
authors.lastname: Ramirez
authors.affiliation: 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.
authors.forename: Rabi
authors.initials: R
authors.lastname: Murad
authors.affiliation: Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Offermanns
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR7104, INSERM U964, Université de Strasbourg, Illkirch 67404, France.
authors.forename: Daniel
authors.identifier: 0000-0002-5555-046X
authors.initials: D
authors.lastname: Metzger
authors.affiliation: 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.
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.affiliation: Center for Tissue Engineering, Department of Plastic Surgery, University of California, Irvine, Irvine, CA 92868, USA.
authors.forename: Alan D
authors.identifier: 0000-0002-5705-8073
authors.initials: AD
authors.lastname: Widgerow
authors.affiliation: 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.
authors.forename: Tai-Lan
authors.identifier: 0000-0002-7746-4677
authors.initials: TL
authors.lastname: Tuan
authors.affiliation: 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.
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authors.initials: A
authors.lastname: Mortazavi
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Rana K
authors.initials: RK
authors.lastname: Gupta
authors.affiliation: 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.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Hamilton
authors.affiliation: Department of Dermatology, Kligman Laboratories, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Millar
authors.affiliation: The Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.|Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Seale
authors.affiliation: Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Warren S
authors.identifier: 0000-0002-2624-0526
authors.initials: WS
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authors.affiliation: The Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.|Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Mitchell A
authors.identifier: 0000-0001-8653-1280
authors.initials: MA
authors.lastname: Lazar
authors.affiliation: 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.
authors.forename: George
authors.identifier: 0000-0003-3534-9408
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authors.lastname: Cotsarelis
mesh_terms: D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D002921:Cicatrix / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000473:pathology; D018859:Hair Follicle / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012038:Regeneration; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014945:Wound Healing
chemical_list: C525718:BMP2 protein, human; C525809:BMP4 protein, human; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C484557:Ebfaz protein, mouse; D011994:Recombinant Proteins; D014157:Transcription Factors