Allele-specific expression reveals genetic drivers of tissue regeneration in mice
Copyright © 2023 Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Cell stem cell - 30(2023), 10 vom: 05. Okt., Seite 1368-1381.e6 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mack, Katya L [VerfasserIn] |
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| Links: |
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| Themen: |
Fibroblasts |
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| Anmerkungen: |
Date Completed 26.10.2023 Date Revised 22.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.stem.2023.08.010 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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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| 700 | 1 | |a Griffin, Michelle F |e verfasserin |4 aut | |
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| 700 | 1 | |a Guardino, Nicholas J |e verfasserin |4 aut | |
| 700 | 1 | |a Spielman, Amanda F |e verfasserin |4 aut | |
| 700 | 1 | |a Davitt, Michael F |e verfasserin |4 aut | |
| 700 | 1 | |a Mascharak, Shamik |e verfasserin |4 aut | |
| 700 | 1 | |a Downer, Mauricio |e verfasserin |4 aut | |
| 700 | 1 | |a Morgan, Annah |e verfasserin |4 aut | |
| 700 | 1 | |a Valencia, Caleb |e verfasserin |4 aut | |
| 700 | 1 | |a Akras, Deena |e verfasserin |4 aut | |
| 700 | 1 | |a Berger, Mark J |e verfasserin |4 aut | |
| 700 | 1 | |a Wan, Derrick C |e verfasserin |4 aut | |
| 700 | 1 | |a Fraser, Hunter B |e verfasserin |4 aut | |
| 700 | 1 | |a Longaker, Michael T |e verfasserin |4 aut | |
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