MicroRNA profiling predicts a variance in the proliferative potential of cardiac progenitor cells derived from neonatal and adult murine hearts

Padmini Sirish, Javier E Lopez, Ning Li, Andrew Wong, Valeriy Timofeyev, J Nilas Young, Maryam Majdi, Ronald A. Li, Huei sheng Vincent Chen, Nipavan Chiamvimonvat

Research output: Contribution to journalArticle

34 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)264-272
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume52
Issue number1
DOIs
StatePublished - Jan 2012

Fingerprint

MicroRNAs
Stem Cells
Myocardium
Regeneration
Cell Proliferation
Proteins
Retinoblastoma
G2 Phase
Cell- and Tissue-Based Therapy
Cell Division
Cell Cycle
Cell Count

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 journalArticle

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. / MicroRNA profiling predicts a variance in the proliferative potential of cardiac progenitor cells derived from neonatal and adult murine hearts. In: Journal of Molecular and Cellular Cardiology. 2012 ; Vol. 52, No. 1. pp. 264-272.
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