Pathologic Stimulus Determines Lineage Commitment of Cardiac C-kit+ Cells
DC Field | Value | Language |
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dc.contributor.author | Chen, Z. | - |
dc.contributor.author | Zhu, W. | - |
dc.contributor.author | Bender, I. | - |
dc.contributor.author | Gong, W. | - |
dc.contributor.author | Kwak, I.-Y. | - |
dc.contributor.author | Yellamilli, A. | - |
dc.contributor.author | Hodges, T.J. | - |
dc.contributor.author | Nemoto, N. | - |
dc.contributor.author | Zhang, J. | - |
dc.contributor.author | Garry, D.J. | - |
dc.contributor.author | van, Berlo J.H. | - |
dc.date.accessioned | 2023-03-08T16:12:13Z | - |
dc.date.available | 2023-03-08T16:12:13Z | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 0009-7322 | - |
dc.identifier.issn | 1524-4539 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/64067 | - |
dc.description.abstract | BACKGROUND: Although cardiac c-kit+ cells are being tested in clinical trials, the circumstances that determine lineage differentiation of c-kit+ cells in vivo are unknown. Recent findings suggest that endogenous cardiac c-kit+ cells rarely contribute cardiomyocytes to the adult heart. We assessed whether various pathological stimuli differentially affect the eventual cell fates of c-kit+ cells.METHODS: We used single-cell sequencing and genetic lineage tracing of c-kit+ cells to determine whether various pathological stimuli would result in different fates of c-kit+ cells.RESULTS: Single-cell sequencing of cardiac CD45-c-kit+ cells showed innate heterogeneity, indicative of the existence of vascular and mesenchymal c-kit+ cells in normal hearts. Cardiac pressure overload resulted in a modest increase in c-kit-derived cardiomyocytes, with significant increases in the numbers of endothelial cells and fibroblasts. Doxorubicin-induced acute cardiotoxicity did not increase c-kit-derived endothelial cell fates but instead induced cardiomyocyte differentiation. Mechanistically, doxorubicin-induced DNA damage in c-kit+ cells resulted in expression of p53. Inhibition of p53 blocked cardiomyocyte differentiation in response to doxorubicin, whereas stabilization of p53 was sufficient to increase c-kit-derived cardiomyocyte differentiation.CONCLUSIONS: These results demonstrate that different pathological stimuli induce different cell fates of c-kit+ cells in vivo. Although the overall rate of cardiomyocyte formation from c-kit+ cells is still below clinically relevant levels, we show that p53 is central to the ability of c-kit+ cells to adopt cardiomyocyte fates, which could lead to the development of strategies to preferentially generate cardiomyocytes from c-kit+ cells. © 2017 American Heart Association, Inc. | - |
dc.format.extent | 14 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.title | Pathologic Stimulus Determines Lineage Commitment of Cardiac C-kit+ Cells | - |
dc.type | Article | - |
dc.identifier.doi | 10.1161/CIRCULATIONAHA.117.030137 | - |
dc.identifier.bibliographicCitation | Circulation, v.136, no.24, pp 2359 - 2372 | - |
dc.description.isOpenAccess | Y | - |
dc.identifier.scopusid | 2-s2.0-85039858464 | - |
dc.citation.endPage | 2372 | - |
dc.citation.number | 24 | - |
dc.citation.startPage | 2359 | - |
dc.citation.title | Circulation | - |
dc.citation.volume | 136 | - |
dc.type.docType | Article | - |
dc.publisher.location | 미국 | - |
dc.subject.keywordAuthor | adult stem cells | - |
dc.subject.keywordAuthor | anthracyclines | - |
dc.subject.keywordAuthor | c-kit | - |
dc.subject.keywordAuthor | heart failure | - |
dc.subject.keywordAuthor | regeneration | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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