Runx1 promotes scar deposition and inhibits myocardial proliferation and survival during zebrafish heart regeneration
Runx1 is a transcription factor that plays a key role in determining the proliferative and differential state of multiple cell types, during both development and adulthood. Here, we report how Runx1 is specifically upregulated at the injury site during zebrafish heart regeneration, and that absence...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Company of Biologists
2020
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| _version_ | 1826305984758284288 |
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| author | Koth, J Wang, X Killen, AC Stockdale, W Potts, HG Jefferson, A Bonkhofer, F Riley, P Patient, R Göttgens, B Mommersteeg, M |
| author_facet | Koth, J Wang, X Killen, AC Stockdale, W Potts, HG Jefferson, A Bonkhofer, F Riley, P Patient, R Göttgens, B Mommersteeg, M |
| author_sort | Koth, J |
| collection | OXFORD |
| description | Runx1 is a transcription factor that plays a key role in determining the proliferative and differential state of multiple cell types, during both development and adulthood. Here, we report how Runx1 is specifically upregulated at the injury site during zebrafish heart regeneration, and that absence of runx1 results in increased myocardial survival and proliferation, and overall heart regeneration, accompanied by decreased fibrosis. Using single cell sequencing, we found that the wild-type injury site consists of Runx1-positive endocardial cells and thrombocytes that induce expression of smooth muscle and collagen genes. Both these populations cannot be identified in runx1 mutant wounds that contain less collagen and fibrin. The reduction in fibrin in the mutant is further explained by reduced myofibroblast formation and upregulation of components of the fibrin degradation pathway, including plasminogen receptor annexin 2A as well as downregulation of plasminogen activator inhibitor serpine1 in myocardium and endocardium, resulting in increased levels of plasminogen. Our findings suggest that Runx1 controls the regenerative response of multiple cardiac cell types and that targeting Runx1 is a novel therapeutic strategy for inducing endogenous heart repair. |
| first_indexed | 2024-03-07T06:41:04Z |
| format | Journal article |
| id | oxford-uuid:f94bbb32-ec30-49b9-83c2-8c72d6c2fd8f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:41:04Z |
| publishDate | 2020 |
| publisher | Company of Biologists |
| record_format | dspace |
| spelling | oxford-uuid:f94bbb32-ec30-49b9-83c2-8c72d6c2fd8f2022-03-27T12:57:00ZRunx1 promotes scar deposition and inhibits myocardial proliferation and survival during zebrafish heart regenerationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f94bbb32-ec30-49b9-83c2-8c72d6c2fd8fEnglishSymplectic ElementsCompany of Biologists2020Koth, JWang, XKillen, ACStockdale, WPotts, HGJefferson, ABonkhofer, FRiley, PPatient, RGöttgens, BMommersteeg, MRunx1 is a transcription factor that plays a key role in determining the proliferative and differential state of multiple cell types, during both development and adulthood. Here, we report how Runx1 is specifically upregulated at the injury site during zebrafish heart regeneration, and that absence of runx1 results in increased myocardial survival and proliferation, and overall heart regeneration, accompanied by decreased fibrosis. Using single cell sequencing, we found that the wild-type injury site consists of Runx1-positive endocardial cells and thrombocytes that induce expression of smooth muscle and collagen genes. Both these populations cannot be identified in runx1 mutant wounds that contain less collagen and fibrin. The reduction in fibrin in the mutant is further explained by reduced myofibroblast formation and upregulation of components of the fibrin degradation pathway, including plasminogen receptor annexin 2A as well as downregulation of plasminogen activator inhibitor serpine1 in myocardium and endocardium, resulting in increased levels of plasminogen. Our findings suggest that Runx1 controls the regenerative response of multiple cardiac cell types and that targeting Runx1 is a novel therapeutic strategy for inducing endogenous heart repair. |
| spellingShingle | Koth, J Wang, X Killen, AC Stockdale, W Potts, HG Jefferson, A Bonkhofer, F Riley, P Patient, R Göttgens, B Mommersteeg, M Runx1 promotes scar deposition and inhibits myocardial proliferation and survival during zebrafish heart regeneration |
| title | Runx1 promotes scar deposition and inhibits myocardial proliferation and survival during zebrafish heart regeneration |
| title_full | Runx1 promotes scar deposition and inhibits myocardial proliferation and survival during zebrafish heart regeneration |
| title_fullStr | Runx1 promotes scar deposition and inhibits myocardial proliferation and survival during zebrafish heart regeneration |
| title_full_unstemmed | Runx1 promotes scar deposition and inhibits myocardial proliferation and survival during zebrafish heart regeneration |
| title_short | Runx1 promotes scar deposition and inhibits myocardial proliferation and survival during zebrafish heart regeneration |
| title_sort | runx1 promotes scar deposition and inhibits myocardial proliferation and survival during zebrafish heart regeneration |
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