Cardiac Sca-1+ cells are not intrinsic stem cells for myocardial development, renewal, and repair

Lu Zhang, Nishat Sultana, Jianyun Yan, Fan Yang, Fuxue Chen, Elena Chepurko, Feng Chun Yang, Qinghua Du, Lior Zangi, Mingjiang Xu, Lei Bu, Chen Leng Cai

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Background: For more than a decade, Sca-1+ cells within the mouse heart have been widely recognized as a stem cell population with multipotency that can give rise to cardiomyocytes, endothelial cells, and smooth muscle cells in vitro and after cardiac grafting. However, the developmental origin and authentic nature of these cells remain elusive. Methods: Here, we used a series of high-fidelity genetic mouse models to characterize the identity and regenerative potential of cardiac resident Sca-1+ cells. Results: With these novel genetic tools, we found that Sca-1 does not label cardiac precursor cells during early embryonic heart formation. Postnatal cardiac resident Sca-1+ cells are in fact a pure endothelial cell population. They retain endothelial properties and exhibit minimal cardiomyogenic potential during development, normal aging and upon ischemic injury. Conclusions: Our study provides definitive insights into the nature of cardiac resident Sca-1+ cells. The observations challenge the current dogma that cardiac resident Sca-1+ cells are intrinsic stem cells for myocardial development, renewal, and repair, and suggest that the mechanisms of transplanted Sca-1+ cells in heart repair need to be reassessed.

Original languageEnglish (US)
Pages (from-to)2919-2930
Number of pages12
JournalCirculation
Volume138
Issue number25
DOIs
StatePublished - 2018

Keywords

  • Heart failure
  • Regeneration
  • Stem cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Zhang, L., Sultana, N., Yan, J., Yang, F., Chen, F., Chepurko, E., Yang, F. C., Du, Q., Zangi, L., Xu, M., Bu, L., & Cai, C. L. (2018). Cardiac Sca-1+ cells are not intrinsic stem cells for myocardial development, renewal, and repair. Circulation, 138(25), 2919-2930. https://doi.org/10.1161/CIRCULATIONAHA.118.035200