期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 52, 期 1, 页码 264-272出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2011.10.012
关键词
Cardiac progenitor cells; c-kit; MicroRNA profiling; Proliferation; miR-17 cluster
资金
- VA
- Howard Hughes Medical Institute
- American Heart Association
- Sarnoff Cardiovascular Research Foundation
- Harold Amos Medical Faculty Development Award
- Robert Wood Johnson Foundation
- California Institute of Regenerative Medicine [RB2-01512, NIH/HL072857]
- [NIH/HL85727]
- [HL85844]
- [NIH/HL105194]
- [T32 DC008072]
Cardiac progenitor cells (CPCs) are multipotent cells that may offer tremendous potentials for the regeneration of injured myocardium. To expand the limited number of CPCs for effective clinical regeneration of myocardium, it is important to understand their proliferative potentials. Single-cell based assays were utilized to purify c-kit(pos) CPCs from human and mouse hearts. MicroRNA profiling identified eight differentially expressed microRNAs in CPCs from neonatal and adult hearts. Notably, the predicted protein targets were predominantly involved in cellular proliferation-related pathways. To directly test this phenotypic prediction, the developmental variance in the proliferation of CPCs was tested. Ki67 protein expression and DNA kinetics were tested in human and mouse in vivo CPCs, and doubling times were tested in primary culture of mouse CPCs. The human embryonic and mouse neonatal CPCs showed a six-fold increase in Ki67 expressing cells, a two-fold increase in the number of cells in S/G2-M phases of cell cycle, and a seven-fold increase in the doubling time in culture when compared to the corresponding adult CPCs. The over-expression of miR-17-92 increased the proliferation in adult CPCs in vivo by two-fold. In addition, the level of retinoblastoma-like 2 (Rb12/p130) protein was two-fold higher in adult compared to neonatal-mouse CPCs. In conclusion, we demonstrate a differentially regulated cohort of microRNAs that predicts differences in cellular proliferation in CPCs during postnatal development and target microRNAs that are involved in this transition. Our study provides new insights that may enhance the utilization of adult CPCs for regenerative therapy of the injured myocardium. (C) 2011 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据