c-kit+ cells minimally contribute cardiomyocytes to the heart

被引:679
作者
van Berlo, Jop H. [1 ,2 ]
Kanisicak, Onur [1 ]
Maillet, Marjorie [1 ]
Vagnozzi, Ronald J. [1 ]
Karch, Jason [1 ]
Lin, Suh-Chin J. [1 ]
Middleton, Ryan C. [3 ]
Marban, Eduardo [3 ]
Molkentin, Jeffery D. [1 ,4 ]
机构
[1] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA
[2] Univ Minnesota, Lillehei Heart Inst, Div Cardiol, Dept Med, Minneapolis, MN 55455 USA
[3] Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA
[4] Cincinnati Childrens Hosp Med Ctr, Howard Hughes Med Inst, Cincinnati, OH 45229 USA
基金
美国国家卫生研究院;
关键词
CARDIAC STEM-CELLS; C-KIT; ADULT; FUSION; REGENERATION; MYOCARDIUM; EXPRESSION; MOUSE; ADOPT;
D O I
10.1038/nature13309
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
If and how the heart regenerates after an injury event is highly debated. c-kit-expressing cardiac progenitor cells have been reported as the primary source for generation of new myocardium after injury. Here we generated two genetic approaches in mice to examine whether endogenous c-kit(+) cells contribute differentiated cardiomyocytes to the heart during development, with ageing or after injury in adulthood. A complementary DNA encoding either Cre recombinase or a tamoxifen-inducible MerCreMer chimaeric protein was targeted to the Kit locus in mice and then bred with reporter lines to permanently mark cell lineage. Endogenous c-kit(+) cells did produce new cardiomyocytes within the heart, although at a percentage of approximately 0.03 or less, and if a preponderance towards cellular fusion is considered, the percentage falls to below approximately 0.008. By contrast, c-kit(+) cells amply generated cardiac endothelial cells. Thus, endogenous c-kit(+) cells cangenerate cardiomyocytes within the heart, although probably at a functionally insignificant level.
引用
收藏
页码:337 / +
页数:16
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