Resident c-kit+ cells in the heart are not cardiac stem cells

Nishat Sultana, Lu Zhang, Jianyun Yan, Jiqiu Chen, Weibin Cai, Shegufta Razzaque, Dongtak Jeong, Wei Sheng, Lei Bu, Mingjiang Xu, Guo-Ying Huang, Roger J. Hajjar, Bin Zhou, Anne Moon and Chen-Leng Cai ()
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Nishat Sultana: The Black Family Stem Cell Institute, and The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai
Lu Zhang: The Black Family Stem Cell Institute, and The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai
Jianyun Yan: The Black Family Stem Cell Institute, and The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai
Jiqiu Chen: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai
Weibin Cai: The Black Family Stem Cell Institute, and The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai
Shegufta Razzaque: The Black Family Stem Cell Institute, and The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai
Dongtak Jeong: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai
Wei Sheng: Cardiovascular Center, Children’s Hospital of Fudan University
Lei Bu: New York University School of Medicine
Mingjiang Xu: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine
Guo-Ying Huang: Cardiovascular Center, Children’s Hospital of Fudan University
Roger J. Hajjar: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai
Bin Zhou: Albert Einstein College of Medicine of Yeshiva University
Anne Moon: Weis Center for Research, Geisinger Clinic
Chen-Leng Cai: The Black Family Stem Cell Institute, and The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: Abstract Identifying a bona fide population of cardiac stem cells (CSCs) is a critical step for developing cell-based therapies for heart failure patients. Previously, cardiac c-kit+ cells were reported to be CSCs with a potential to become myocardial, endothelial and smooth muscle cells in vitro and after cardiac injury. Here we provide further insights into the nature of cardiac c-kit+ cells. By targeting the c-kit locus with multiple reporter genes in mice, we find that c-kit expression rarely co-localizes with the expression of the cardiac progenitor and myogenic marker Nkx2.5, or that of the myocardial marker, cardiac troponin T (cTnT). Instead, c-kit predominantly labels a cardiac endothelial cell population in developing and adult hearts. After acute cardiac injury, c-kit+ cells retain their endothelial identity and do not become myogenic progenitors or cardiomyocytes. Thus, our work strongly suggests that c-kit+ cells in the murine heart are endothelial cells and not CSCs.

Date: 2015
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DOI: 10.1038/ncomms9701

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