生物
再生(生物学)
伤口愈合
细胞生物学
异位表达
成纤维细胞
皮肤修复
基因
免疫系统
等位基因
免疫学
遗传学
细胞培养
作者
Katya L. Mack,Heather E. Talbott,Michelle Griffin,J. M. R. Parker,Nicholas Guardino,Amanda Spielman,Michael F. Davitt,Shamik Mascharak,Mauricio Downer,Annah Morgan,C. Alexander Valencia,Deena Akras,Mark J. Berger,Derrick C. Wan,Hunter B. Fraser,Michael T. Longaker
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2023-10-01
卷期号:30 (10): 1368-1381.e6
被引量:2
标识
DOI:10.1016/j.stem.2023.08.010
摘要
In adult mammals, skin wounds typically heal by scarring rather than through regeneration. In contrast, "super-healer" Murphy Roths Large (MRL) mice have the unusual ability to regenerate ear punch wounds; however, the molecular basis for this regeneration remains elusive. Here, in hybrid crosses between MRL and non-regenerating mice, we used allele-specific gene expression to identify cis-regulatory variation associated with ear regeneration. Analyzing three major cell populations (immune, fibroblast, and endothelial), we found that genes with cis-regulatory differences specifically in fibroblasts were associated with wound-healing pathways and also co-localized with quantitative trait loci for ear wound-healing. Ectopic treatment with one of these proteins, complement factor H (CFH), accelerated wound repair and induced regeneration in typically fibrotic wounds. Through single-cell RNA sequencing (RNA-seq), we observed that CFH treatment dramatically reduced immune cell recruitment to wounds, suggesting a potential mechanism for CFH's effect. Overall, our results provide insights into the molecular drivers of regeneration with potential clinical implications.
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