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

TitleMicroRNA profiling predicts a variance in the proliferative potential of cardiac progenitor cells derived from neonatal and adult murine hearts
Authors
Issue Date2012
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yjmcc
Citation
Journal Of Molecular And Cellular Cardiology, 2012, v. 52 n. 1, p. 264-272 How to Cite?
AbstractCardiac 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. © 2011 Elsevier Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/163441
ISSN
2015 Impact Factor: 4.874
2015 SCImago Journal Rankings: 2.522
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSirish, Pen_US
dc.contributor.authorLópez, JEen_US
dc.contributor.authorLi, Nen_US
dc.contributor.authorWong, Aen_US
dc.contributor.authorTimofeyev, Ven_US
dc.contributor.authorYoung, JNen_US
dc.contributor.authorMajdi, Men_US
dc.contributor.authorLi, RAen_US
dc.contributor.authorChen, HSVen_US
dc.contributor.authorChiamvimonvat, Nen_US
dc.date.accessioned2012-09-05T05:31:24Z-
dc.date.available2012-09-05T05:31:24Z-
dc.date.issued2012en_US
dc.identifier.citationJournal Of Molecular And Cellular Cardiology, 2012, v. 52 n. 1, p. 264-272en_US
dc.identifier.issn0022-2828en_US
dc.identifier.urihttp://hdl.handle.net/10722/163441-
dc.description.abstractCardiac 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. © 2011 Elsevier Ltd.en_US
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yjmccen_US
dc.relation.ispartofJournal of Molecular and Cellular Cardiologyen_US
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in Journal of Molecular and Cellular Cardiology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Molecular and Cellular Cardiology, [VOL 52, ISSUE 1, 2012] DOI 10.1016/j.yjmcc.2011.10.012-
dc.subject.meshAnimalsen_US
dc.subject.meshCell Cycle - Physiologyen_US
dc.subject.meshCell Proliferationen_US
dc.subject.meshCell Separationen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshCluster Analysisen_US
dc.subject.meshGene Expression Profilingen_US
dc.subject.meshHumansen_US
dc.subject.meshKineticsen_US
dc.subject.meshMiceen_US
dc.subject.meshMicrornas - Genetics - Metabolismen_US
dc.subject.meshMyoblasts, Cardiac - Metabolismen_US
dc.subject.meshPhenotypeen_US
dc.subject.meshProto-Oncogene Proteins C-Kit - Metabolismen_US
dc.subject.meshRetinoblastoma-Like Protein P130 - Metabolismen_US
dc.titleMicroRNA profiling predicts a variance in the proliferative potential of cardiac progenitor cells derived from neonatal and adult murine heartsen_US
dc.typeArticleen_US
dc.identifier.emailLi, RA:ronaldli@hkucc.hku.hken_US
dc.identifier.authorityLi, RA=rp01352en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1016/j.yjmcc.2011.10.012en_US
dc.identifier.pmid22062954-
dc.identifier.pmcidPMC3362795-
dc.identifier.scopuseid_2-s2.0-84155188929en_US
dc.identifier.hkuros212205-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84155188929&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume52en_US
dc.identifier.issue1en_US
dc.identifier.spage264en_US
dc.identifier.epage272en_US
dc.identifier.isiWOS:000303275000030-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridSirish, P=36873197300en_US
dc.identifier.scopusauthoridLópez, JE=36986226000en_US
dc.identifier.scopusauthoridLi, N=36014373300en_US
dc.identifier.scopusauthoridWong, A=54790379900en_US
dc.identifier.scopusauthoridTimofeyev, V=8966886700en_US
dc.identifier.scopusauthoridYoung, JN=8277142200en_US
dc.identifier.scopusauthoridMajdi, M=36981350100en_US
dc.identifier.scopusauthoridLi, RA=7404724466en_US
dc.identifier.scopusauthoridChen, HSV=52663310300en_US
dc.identifier.scopusauthoridChiamvimonvat, N=7004461965en_US
dc.identifier.citeulike9949531-

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