Volume 26, No 1, Jan 2016
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 26 Issue 1, January 2016: 119-130 | Open Access
ORIGINAL ARTICLES
Genetic lineage tracing identifies in situ Kit-expressing cardiomyocytes
Qiaozhen Liu1,*, Rui Yang1,*, Xiuzhen Huang1, Hui Zhang1, Lingjuan He1, Libo Zhang1, Xueying Tian1, Yu Nie2, Shengshou Hu2, Yan Yan3, Li Zhang4, Zengyong Qiao5, Qing-Dong Wang6, Kathy O Lui7 and Bin Zhou1,8,9
1Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
2State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
3Zhongshan Hospital, Fudan University, Shanghai 200032, China
4Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, China
5Department of Cardiovascular Medicine, Southern Medical University Affiliated Fengxian Hospital, Shanghai 201499, China
6Cardiovascular and Metabolic Diseases Innovative Medicines, AstraZeneca, Mölndal 43183, Sweden
7Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR 999077, China
8Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
9ShanghaiTech University, Shanghai 201210, China
Correspondence: Bin Zhou, Tel: +86-21-54920974(zhoubin@sibs.ac.cn)
Cardiac cells marked by c-Kit or Kit, dubbed cardiac stem cells (CSCs), are in clinical trials to investigate their ability to stimulate cardiac regeneration and repair. These studies were initially motivated by the purported cardiogenic activity of these cells. Recent lineage tracing studies using Kit promoter to drive expression of the inducible Cre recombinase showed that these CSCs had highly limited cardiogenic activity, inadequate to support efficient cardiac repair. Here we reassess the lineage tracing data by investigating the identity of cells immediately after Cre labeling. Our instant lineage tracing approach identifies Kit-expressing cardiomyocytes, which are labeled immediately after tamoxifen induction. In combination with long-term lineage tracing experiments, these data reveal that the large majority of long-term labeled cardiomyocytes are pre-existing Kit-expressing cardiomyocytes rather than cardiomyocytes formed de novo from CSCs. This study presents a new interpretation for the contribution of Kit+ cells to cardiomyocytes and shows that Kit genetic lineage tracing over-estimates the cardiogenic activity of Kit+ CSCs.
10.1038/cr.2015.143
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