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Regeneration of fat cells from myofibroblasts during wound healing

2017; American Association for the Advancement of Science; Volume: 355; Issue: 6326 Linguagem: Inglês

10.1126/science.aai8792

1095-9203

Maksim V. Plikus, Christian F. Guerrero‐Juarez, Mayumi Ito, Leslie A. Lange, Priya H. Dedhia, Ying Zheng, Mengle Shao, Denise Gay, Raúl Ramos, Tsai‐Ching Hsi, Ji Won Oh, Xiaojie Wang, Amanda Ramirez, Sara E. Konopelski, Arijh Elzein, Anne Wang, Rarinthip June Supapannachart, Hye-Lim Lee, Chae Ho Lim, Arben Nace, Amy Guo, Elsa Treffeisen, Thomas Andl, Ricardo N. Ramírez, Rabi Murad, Stefan Offermanns, Daniel Metzger, Pierre Chambon, Alan D. Widgerow, Tai‐Lan Tuan, A Mortazavi, Rana K. Gupta, Bruce A. Hamilton, Sarah E. Millar, Patrick Seale, Warren S. Pear, Mitchell A. Lazar, George Cotsarelis,

Nerve injury and regeneration

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.