Regeneration of fat cells from myofibroblasts during wound healing

Maksim V. Plikus, Christian F. Guerrero-Juarez, Mayumi Ito, Yun Rose Li, Priya H. Dedhia, Ying Zheng, Mengle Shao, Denise L. Gay, Raul 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 NaceAmy Guo, Elsa Treffeisen, Thomas Andl, Ricardo N. Ramirez, Rabi Murad, Stefan Offermanns, Daniel Metzger, Pierre Chambon, Alan D. Widgerow, Tai Lan Tuan, Ali Mortazavi, Rana K Gupta, Bruce A. Hamilton, Sarah E. Millar, Patrick Seale, Warren S. Pear, Mitchell A. Lazar, George Cotsarelis

Research output: Contribution to journalArticle

115 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)748-752
Number of pages5
JournalScience
Volume355
Issue number6326
DOIs
StatePublished - Feb 17 2017

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Myofibroblasts
Adipocytes
Wound Healing
Bone Morphogenetic Proteins
Hair Follicle
Regeneration
Bone Morphogenetic Protein Receptors
Keloid
Amphibians
Cell Lineage
Plastics
Cicatrix
Mammals
Fishes
Transcription Factors
Fibroblasts

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Plikus, M. V., Guerrero-Juarez, C. F., Ito, M., Li, Y. R., Dedhia, P. H., Zheng, Y., ... Cotsarelis, G. (2017). Regeneration of fat cells from myofibroblasts during wound healing. Science, 355(6326), 748-752. https://doi.org/10.1126/science.aai8792

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

In: Science, Vol. 355, No. 6326, 17.02.2017, p. 748-752.

Research output: Contribution to journalArticle

Plikus, MV, Guerrero-Juarez, CF, Ito, M, Li, YR, Dedhia, PH, Zheng, Y, Shao, M, Gay, DL, Ramos, R, Hsi, TC, Oh, JW, Wang, X, Ramirez, A, Konopelski, SE, Elzein, A, Wang, A, Supapannachart, RJ, Lee, HL, Lim, CH, Nace, A, Guo, A, Treffeisen, E, Andl, T, Ramirez, RN, Murad, R, Offermanns, S, Metzger, D, Chambon, P, Widgerow, AD, Tuan, TL, Mortazavi, A, Gupta, RK, Hamilton, BA, Millar, SE, Seale, P, Pear, WS, Lazar, MA & Cotsarelis, G 2017, 'Regeneration of fat cells from myofibroblasts during wound healing', Science, vol. 355, no. 6326, pp. 748-752. https://doi.org/10.1126/science.aai8792
Plikus MV, Guerrero-Juarez CF, Ito M, Li YR, Dedhia PH, Zheng Y et al. Regeneration of fat cells from myofibroblasts during wound healing. Science. 2017 Feb 17;355(6326):748-752. https://doi.org/10.1126/science.aai8792
Plikus, Maksim V. ; Guerrero-Juarez, Christian F. ; Ito, Mayumi ; Li, Yun Rose ; Dedhia, Priya H. ; Zheng, Ying ; Shao, Mengle ; Gay, Denise L. ; Ramos, Raul ; Hsi, Tsai Ching ; Oh, Ji Won ; Wang, Xiaojie ; Ramirez, Amanda ; Konopelski, Sara E. ; Elzein, Arijh ; Wang, Anne ; Supapannachart, Rarinthip June ; Lee, Hye Lim ; Lim, Chae Ho ; Nace, Arben ; Guo, Amy ; Treffeisen, Elsa ; Andl, Thomas ; Ramirez, Ricardo N. ; Murad, Rabi ; Offermanns, Stefan ; Metzger, Daniel ; Chambon, Pierre ; Widgerow, Alan D. ; Tuan, Tai Lan ; Mortazavi, Ali ; Gupta, Rana K ; Hamilton, Bruce A. ; Millar, Sarah E. ; Seale, Patrick ; Pear, Warren S. ; Lazar, Mitchell A. ; Cotsarelis, George. / Regeneration of fat cells from myofibroblasts during wound healing. In: Science. 2017 ; Vol. 355, No. 6326. pp. 748-752.
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AU - Ramirez, Ricardo N.

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AU - Chambon, Pierre

AU - Widgerow, Alan D.

AU - Tuan, Tai Lan

AU - Mortazavi, Ali

AU - Gupta, Rana K

AU - Hamilton, Bruce A.

AU - Millar, Sarah E.

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