Abstract
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 (Rbl2/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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 264-272 |
| Number of pages | 9 |
| Journal | Journal of Molecular and Cellular Cardiology |
| Volume | 52 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2012 |
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Keywords
- C-kit
- Cardiac progenitor cells
- MicroRNA profiling
- MiR-17 cluster
- Proliferation
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine
Cite this
MicroRNA profiling predicts a variance in the proliferative potential of cardiac progenitor cells derived from neonatal and adult murine hearts. / Sirish, Padmini; Lopez, Javier E; Li, Ning; Wong, Andrew; Timofeyev, Valeriy; Young, J Nilas; Majdi, Maryam; Li, Ronald A.; Chen, Huei sheng Vincent; Chiamvimonvat, Nipavan.
In: Journal of Molecular and Cellular Cardiology, Vol. 52, No. 1, 01.2012, p. 264-272.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MicroRNA profiling predicts a variance in the proliferative potential of cardiac progenitor cells derived from neonatal and adult murine hearts
AU - Sirish, Padmini
AU - Lopez, Javier E
AU - Li, Ning
AU - Wong, Andrew
AU - Timofeyev, Valeriy
AU - Young, J Nilas
AU - Majdi, Maryam
AU - Li, Ronald A.
AU - Chen, Huei sheng Vincent
AU - Chiamvimonvat, Nipavan
PY - 2012/1
Y1 - 2012/1
N2 - 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 (Rbl2/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.
AB - 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 (Rbl2/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.
KW - C-kit
KW - Cardiac progenitor cells
KW - MicroRNA profiling
KW - MiR-17 cluster
KW - Proliferation
UR - http://www.scopus.com/inward/record.url?scp=84155188929&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84155188929&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2011.10.012
DO - 10.1016/j.yjmcc.2011.10.012
M3 - Article
C2 - 22062954
AN - SCOPUS:84155188929
VL - 52
SP - 264
EP - 272
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
IS - 1
ER -