Functional cardiomyocytes derived from Isl1 cardiac progenitors via Bmp4 stimulation

dc.authorid0000-0002-7199-583X
dc.contributor.authorÇağavi, Esra
dc.contributor.authorBartulos, Oscar
dc.contributor.authorSuh, Carol Young
dc.contributor.authorSun, Baonan
dc.contributor.authorYue, Zhichao
dc.contributor.authorJiang, Zhengxin
dc.contributor.authorYue, Lixia
dc.contributor.authorQyang, Yibing
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T20:02:37Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T20:02:37Z
dc.date.issued2014
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalı
dc.descriptionWOS: 000348845600001
dc.descriptionPubMed ID: 25522363
dc.description.abstractAs heart failure due to myocardial infarction remains a leading cause of morbidity worldwide, cell-based cardiac regenerative therapy using cardiac progenitor cells (CPCs) could provide a potential treatment for the repair of injured myocardium. As adult CPCs may have limitations regarding tissue accessibility and proliferative ability, CPCs derived from embryonic stem cells (ESCs) could serve as an unlimited source of cells with high proliferative ability. As one of the CPCs that can be derived from embryonic stem cells, Isl1 expressing cardiac progenitor cells (Isl1-CPCs) may serve as a valuable source of cells for cardiac repair due to their high cardiac differentiation potential and authentic cardiac origin. In order to generate an unlimited number of Isl1-CPCs, we used a previously established an ESC line that allows for isolation of Isl1-CPCs by green fluorescent protein (GFP) expression that is directed by the mef2c gene, specifically expressed in the Isl1 domain of the anterior heart field. To improve the efficiency of cardiac differentiation of Isl1-CPCs, we studied the role of Bmp4 in cardiogenesis of Isl1-CPCs. We show an inductive role of Bmp directly on cardiac progenitors and its enhancement on early cardiac differentiation of CPCs. Upon induction of Bmp4 to Isl1-CPCs during differentiation, the cTnT+ cardiomyocyte population was enhanced 2.8 +/- 0.4 fold for Bmp4 treated CPC cultures compared to that detected for vehicle treated cultures. Both Bmp4 treated and untreated cardiomyocytes exhibit proper electrophysiological and calcium signaling properties. In addition, we observed a significant increase in Tbx5 and Tbx20 expression in differentiation cultures treated with Bmp4 compared to the untreated control, suggesting a link between Bmp4 and Tbx genes which may contribute to the enhanced cardiac differentiation in Bmp4 treated cultures. Collectively these findings suggest a cardiomyogenic role for Bmp4 directly on a pure population of Isl1 expressing cardiac progenitors, which could lead to enhancement of cardiac differentiation and engraftment, holding a significant therapeutic value for cardiac repair in the future.
dc.description.sponsorshipAmerican Heart Association [09SDG2080420]en_US
dc.description.sponsorshipConnecticut Stem Cell Program [09SCAYALE10]-[10SCA35]-[11SCB18]en_US
dc.description.sponsorshipUnited States Department of Health & Human Services-National Institutes of Health (NIH) - USA [1K02HL116705-01]-[UL1 RR024139]-[R01HL078960]en_US
dc.description.sponsorshipNational Science Foundation (NSF) [DGE-1122492]en_US
dc.description.sponsorshipThis work was supported by AHA 09SDG2080420 (http://www.heart.org/HEARTORG/), Connecticut Stem Cell Program 09SCAYALE10, 10SCA35, 11SCB18 (http://www.ct.gov/dph/cwp/view.asp?a=3142&q=389700), NIH 1K02HL116705-01 and NIH UL1 RR024139/CTSA Scholar Award (http://grants.nih.gov/grants/guide/index.html)(Y. Qyang), National Science Foundation Graduate Research Fellowship DGE-1122492 (http://www.nsfgrfp.org/)(C. Suh) and NIH R01HL078960 (http://grants.nih.gov/grants/guide/index.html)(L. Yue). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.identifier.citationÇağavi, E., Bartulos, O., Suh, C. Y., Sun, B., Yue, Z., Jiang, Z. ... Qyang, Y. (2014). Functional cardiomyocytes derived from Isl1 cardiac progenitors via Bmp4 stimulation. PLoS One, 9(12). https://dx.doi.org/10.1371/journal.pone.0110752
dc.identifier.doi10.1371/journal.pone.0110752
dc.identifier.issn1932-6203
dc.identifier.issue12
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://dx.doi.org/10.1371/journal.pone.0110752
dc.identifier.urihttps://hdl.handle.net/20.500.12511/3692
dc.identifier.volume9
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherPublic Library of Science
dc.relation.ispartofPLoS Oneen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsAttribution 4.0 International*
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectFunctional Cardiomyocytes
dc.subjectIsl1
dc.subjectBmp4
dc.titleFunctional cardiomyocytes derived from Isl1 cardiac progenitors via Bmp4 stimulation
dc.typeArticle

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