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

PDGFA regulation of dermal adipocyte stem cells

“…During wound healing, defects in adipogenesis can abrogate fibroblast recruitment into wound beds, leading to defects in extracellular matrix deposition and tissue repair (3). Migration of adipocyte precursors into the wounded area might also contribute to the mesenchymal repopulation of the wounded site (4) and in wounds where hair follicle neogenesis is observed fully functional adipocyte precursors are present (5). These findings highlight the breadth of the role of adipose tissue in the skin.…”

Fibroblast heterogeneity: implications for human disease

“…Interestingly, a recent study has demonstrated that myofibroblasts have the capacity to transdifferentiate to adipocytes in response to bone morphogenetic protein (BMP) signals arising from hair follicles in the healing wound (85), suggesting that preadipocytes are not the only cell type that can give rise to mature fat cells in the dermis.…”

Signature Genes in Macrodactyly through Transcriptome Network Analysis Reveal their Association of Lipid Metabolism

“…There is a small number of hair follicles with very sparse density in the normal hand and foot, compared with the rest of the body. We recently reported that fat regeneration can be committed through hair follicles and finely regulated by myofibroblasts [13]. Simultaneously, in human, subcutaneous fat regeneration is highly synchronized with the cyclic patterns of hair follicles [27].…”

“…We employed and modified the methods previously reported by our group [13][14][15]. First, we sorted the expression data in excel sheet.…”

“…Recently, our group also found the novel mechanistic insight using meta-analysis of the high throughput data [13,14]. Utilizing the bioinformatical network analysis of differentially expressed genes (DEGs), researcher can find the distinct molecular network connectivities, induced by the unique microenvironments of the disease and physiologic conditions [13][14][15][16].…”