生物
伤口愈合
间充质干细胞
细胞生物学
肌成纤维细胞
再生(生物学)
祖细胞
纤维化
毛囊
干细胞
癌症研究
再生医学
免疫学
病理
医学
作者
Sepideh Abbasi,Sarthak Sinha,Elodie Labit,Nicole L. Rosin,Grace Yoon,Waleed Rahmani,Arzina Jaffer,Nilesh Sharma,Andrew Hagner,Prajay Shah,Rohit Arora,Jessica Yoon,Anowara Islam,Aya Uchida,Chih Kai Chang,Jo Anne Stratton,R. Wilder Scott,Fábio Rossi,T. Michael Underhill,Jeff Biernaskie
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2020-09-01
卷期号:27 (3): 396-412.e6
被引量:115
标识
DOI:10.1016/j.stem.2020.07.008
摘要
Dermal fibroblasts exhibit considerable heterogeneity during homeostasis and in response to injury. Defining lineage origins of reparative fibroblasts and regulatory programs that drive fibrosis or, conversely, promote regeneration will be essential for improving healing outcomes. Using complementary fate-mapping approaches, we show that hair follicle mesenchymal progenitors make limited contributions to wound repair. In contrast, extrafollicular progenitors marked by the quiescence-associated factor Hic1 generated the bulk of reparative fibroblasts and exhibited functional divergence, mediating regeneration in the center of the wound neodermis and scar formation in the periphery. Single-cell RNA-seq revealed unique transcriptional, regulatory, and epithelial-mesenchymal crosstalk signatures that enabled mesenchymal competence for regeneration. Integration with scATAC-seq highlighted changes in chromatin accessibility within regeneration-associated loci. Finally, pharmacological modulation of RUNX1 and retinoic acid signaling or genetic deletion of Hic1 within wound-activated fibroblasts was sufficient to modulate healing outcomes, suggesting that reparative fibroblasts have latent but modifiable regenerative capacity.
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