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Regeneration of fat cells from myofibroblasts during wound healing

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

in Adipocytes / Adipocytes - physiology / Amphibians / Animals / Bone Morphogenetic Protein 2 - pharmacology / Bone Morphogenetic Protein 4 - pharmacology / Bone morphogenetic proteins / Bone Morphogenetic Proteins - metabolism / Bones / Cells, Cultured / Cellular Biology / Cellular Reprogramming / Cicatrix - pathology / Deletion / DNA-Binding Proteins - metabolism / Fibroblasts / Fibroblasts - pathology / Formations / Hair / Hair Follicle - physiology / Hair loss / Humans / In vitro methods and tests / Life Sciences / Limbs / Lipids / Mammals / Mice / Mice, Inbred C57BL / Myofibroblasts - drug effects / Myofibroblasts - physiology / Proteins / Recombinant Proteins - pharmacology / Regeneration / Rodents / Scars / Signal Transduction / Transcription factors / Transcription Factors - metabolism / Wound Healing

2017

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Regeneration of fat cells from myofibroblasts during wound healing

2017

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2017

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Journal Article

Regeneration of fat cells from myofibroblasts during wound healing

Konopelski, Sara E.,

Andl, Thomas,

Ramirez, Ricardo N.,

Murad, Rabi,

Metzger, Daniel,

Gupta, Rana K.,

Elzein, Arijh,

Zheng, Ying,

Chambon, Pierre,

Dedhia, Priya H.,

Lazar, Mitchell A.,

Seale, Patrick,

Nace, Arben,

Widgerow, Alan D.,

Tuan, Tai-Lan,

Pear, Warren S.,

Wang, Xiaojie,

Guerrero-Juarez, Christian F.,

Shao, Mengle,

Wang, Anne,

Offermanns, Stefan,

Millar, Sarah E.,

Guo, Amy,

Lim, Chae Ho,

Lee, Hye-Lim,

Oh, Ji Won,

Hamilton, Bruce A.,

Li, Yun Rose,

Cotsarelis, George,

Supapannachart, Rarinthip June,

Ramos, Raul,

Gay, Denise L.,

Ramirez, Amanda,

Plikus, Maksim V.,

Ito, Mayumi,

Treffeisen, Elsa,

Hsi, Tsai-Ching,

Mortazavi, Ali

2017

Overview

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.

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Publisher

American Association for the Advancement of Science,The American Association for the Advancement of Science,American Association for the Advancement of Science (AAAS)

Subject

Adipocytes

/ Adipocytes - physiology

/ Amphibians

/ Animals

/ Bone Morphogenetic Protein 2 - pharmacology

/ Bone Morphogenetic Protein 4 - pharmacology

/ Bone morphogenetic proteins

/ Bone Morphogenetic Proteins - metabolism

/ Bones

/ Cells, Cultured

/ Cellular Biology