Lu Zhang1,2, Nishat Sultana2,3, Jianyun Yan4, Fan Yang1,2, Fuxue Chen5, Elena Chepurko3, Feng-Chun Yang6, Qinghua Du6, Lior Zangi3, Mingjiang Xu6, Lei Bu7, Chen-Leng Cai1,2. 1. Riley Heart Research Center and Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis (L. Zhang, F.Y., C.-L.C.). 2. Department of Developmental and Regenerative Biology and The Black Family Stem Cell Institute (L. Zhang, N.S., F.Y., C.-L.C.), Icahn School of Medicine at Mount Sinai, New York. 3. Department of Medicine and Cardiovascular Research Center (N.S., E.C., L. Zangi), Icahn School of Medicine at Mount Sinai, New York. 4. Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, and Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Guangzhou, China (J.Y.). 5. College of Life Sciences, Shanghai University, China (F.C.). 6. Department of Biochemistry and Molecular Biology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, FL (F.-C.Y., Q.D., M.X.). 7. Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY (L.B.).
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.
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.
Authors: Sophy A Jesty; Michele A Steffey; Frank K Lee; Martin Breitbach; Michael Hesse; Shaun Reining; Jane C Lee; Robert M Doran; Alexander Yu Nikitin; Bernd K Fleischmann; Michael I Kotlikoff Journal: Proc Natl Acad Sci U S A Date: 2012-07-30 Impact factor: 11.205
Authors: Kalpaj R Parekh; Janna Nawroth; Albert Pai; Shana M Busch; Christiana N Senger; Amy L Ryan Journal: Am J Physiol Cell Physiol Date: 2020-08-12 Impact factor: 4.249