@article{607913b0b22946fc83d1eea06d3362a9,
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.",
author = "Plikus, {Maksim V.} and Guerrero-Juarez, {Christian F.} and Mayumi Ito and Li, {Yun Rose} and Dedhia, {Priya H.} and Ying Zheng and Mengle Shao and Gay, {Denise L.} and Raul Ramos and Hsi, {Tsai Ching} and Oh, {Ji Won} and Xiaojie Wang and Amanda Ramirez and Konopelski, {Sara E.} and Arijh Elzein and Anne Wang and Supapannachart, {Rarinthip June} and Lee, {Hye Lim} and Lim, {Chae Ho} and Arben Nace and Amy Guo and Elsa Treffeisen and Thomas Andl and Ramirez, {Ricardo N.} and Rabi Murad and Stefan Offermanns and Daniel Metzger and Pierre Chambon and Widgerow, {Alan D.} and Tuan, {Tai Lan} and Ali Mortazavi and Gupta, {Rana K} and Hamilton, {Bruce A.} and Millar, {Sarah E.} and Patrick Seale and Pear, {Warren S.} and Lazar, {Mitchell A.} and George Cotsarelis",
note = "Funding Information: Funding is provided by U.S. NIH grant R01-AR055309, NIH Skin Diseases Research Core grant P30-AR057217, and the Edward and Fannie Gray Hall Center for Human Appearance. M.V.P. is supported by a pilot grant from the Diabetes and Endocrinology Research Center (University of Pennsylvania), a Dermatology Foundation research grant, an Edward Mallinckrodt Jr. Foundation grant, a Pew Charitable Trust grant, and NIH grants R01-AR067273 and R01-AR069653. M.A.L. is supported by NIH grant DK49210, M.I. by NIH grant R01-AR066022, S.E.M. by NIH grant R37-AR047709 and Penn Skin Biology and Diseases Resource-based Core grant P30-AR069589, W.S.P. by NIH grant R01-AI047833, R.K.G. by NIH grant R01-DK104789, T.-L.T. by NIH grant R01-GM095821, B.A.H. by NIH grant R01-NS05487, R.R. by California Institute for Regenerative Medicine training grant TG2-01152, C.F.G.-J. by the NSF Graduate Research Fellowship Program (DGE-1321846) and a training grant from MBRS-IMSD (Initiative for Maximizing Student Development; GM055246), X.W. by a Canadian Institutes of Health Research postdoctoral fellowship (MFE-123724), J.W.O. by National Research Foundation of Korea grant 2016R1C1B1015211, C.H.L. by the Cutaneous Biology and Skin Disease training program (T32-AR064184), Y.R.L. by a NIH National Research Service Award F30 training grant and a Paul and Daisy Soros Fellowship for New Americans, H.-L.L. by NIH T32 training grant T32-CA009054-37, and M.S. by American Heart Association postdoctoral fellowship 16POST26420136. Retn-lacZ mice were generated with the Transgenic Mouse Core of the University of Pennsylvania Diabetes Research Center (NIH grant DK19525). We thank Y. Mishina for providing Bmpr1aflox mice, C.-M. Chuong for providing K14-Noggin mice, V. Scarfone and C. Tu for their assistance with fluorescence-activated cell sorting and tissue culture, Z. Yang for technical assistance, and P. Sterling for reviewing the manuscript. SMA-CreERT2 mice are available from P.C. under a material transfer agreement with the University of California, Irvine. P.C. and D.M. are inventors on patents EP 1 692 936 B1 and US 7112715 B2, held by GIE-CERBM (Centre Europ{\'e}en de Recherche en Biologie et M{\'e}decine), that cover the method for generating conditional DNA recombination in mice by using the Cre-ERT2 fusion protein. M.V.P., C.F.G.-J., and G.C. are co-inventors on a patent application filed through the U.S. Patent and Trademark Office by the University of Pennsylvania describing the BMP pathway as a target for promoting neogenic fat formation, among other claims. Publisher Copyright: {\textcopyright} 2017, American Association for the Advancement of Science. All rights reserved.",
year = "2017",
month = feb,
day = "17",
doi = "10.1126/science.aai8792",
language = "English (US)",
volume = "355",
pages = "748--752",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6326",
}