| First Author | Mack KL | Year | 2023 |
| Journal | Cell Stem Cell | Volume | 30 |
| Issue | 10 | Pages | 1368-1381.e6 |
| PubMed ID | 37714154 | Mgi Jnum | J:357878 |
| Mgi Id | MGI:7538775 | Doi | 10.1016/j.stem.2023.08.010 |
| Citation | Mack KL, et al. (2023) Allele-specific expression reveals genetic drivers of tissue regeneration in mice. Cell Stem Cell 30(10):1368-1381.e6 |
| abstractText | 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. |
