title: Resident c-kit(+) cells in the heart are not cardiac stem cells.
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.
authors.affiliation: Department of Developmental and Regenerative Biology, The Black Family Stem Cell Institute, and The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Nishat
authors.initials: N
authors.lastname: Sultana
authors.affiliation: Department of Developmental and Regenerative Biology, The Black Family Stem Cell Institute, and The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Developmental and Regenerative Biology, The Black Family Stem Cell Institute, and The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Medicine, Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Jiqiu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Developmental and Regenerative Biology, The Black Family Stem Cell Institute, and The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Weibin
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Developmental and Regenerative Biology, The Black Family Stem Cell Institute, and The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Shegufta
authors.initials: S
authors.lastname: Razzaque
authors.affiliation: Department of Medicine, Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Dongtak
authors.initials: D
authors.lastname: Jeong
authors.affiliation: Cardiovascular Center, Children's Hospital of Fudan University, Shanghai 201102, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sheng
authors.affiliation: Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Bu
authors.affiliation: Department of Biochemistry and Molecular Biology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
authors.forename: Mingjiang
authors.initials: M
authors.lastname: Xu
authors.affiliation: Cardiovascular Center, Children's Hospital of Fudan University, Shanghai 201102, China.
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Huang
authors.affiliation: Department of Medicine, Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Moon
authors.affiliation: Department of Developmental and Regenerative Biology, The Black Family Stem Cell Institute, and The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Chen-Leng
authors.initials: CL
authors.lastname: Cai
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D014157:Transcription Factors; D019009:Proto-Oncogene Proteins c-kit