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Article: Exogenous expression of human apoA-I enhances cardiac differentiation of pluripotent stem cells

TitleExogenous expression of human apoA-I enhances cardiac differentiation of pluripotent stem cells
Authors
Issue Date2011
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2011, v. 6 n. 5 How to Cite?
AbstractThe cardioprotective effects of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA-I) are well documented, but their effects in the direction of the cardiac differentiation of embryonic stem cells are unknown. We evaluated the effects of exogenous apoA-I expression on cardiac differentiation of ESCs and maturation of ESC-derived cardiomyocytes. We stably over-expressed full-length human apoA-I cDNA with lentivirus (LV)-mediated gene transfer in undifferentiated mouse ESCs and human induced pluripotent stem cells. Upon cardiac differentiation, we observed a significantly higher percentage of beating embryoid bodies, an increased number of cardiomyocytes as determined by flow cytometry, and expression of cardiac markers including α-myosin heavy chain, β-myosin heavy chain and myosin light chain 2 ventricular transcripts in LV-apoA-I transduced ESCs compared with control (LV-GFP). In the presence of noggin, a BMP4 antagonist, activation of BMP4-SMAD signaling cascade in apoA-I transduced ESCs completely abolished the apoA-I stimulated cardiac differentiation. Furthermore, co-application of recombinant apoA-I and BMP4 synergistically increased the percentage of beating EBs derived from untransduced D3 ESCs. These together suggests that that pro-cardiogenic apoA-I is mediated via the BMP4-SMAD signaling pathway. Functionally, cardiomyocytes derived from the apoA-I-transduced cells exhibited improved calcium handling properties in both non-caffeine and caffeine-induced calcium transient, suggesting that apoA-I plays a role in enhancing cardiac maturation. This increased cardiac differentiation and maturation has also been observed in human iPSCs, providing further evidence of the beneficial effects of apoA-I in promoting cardiac differentiation. In Conclusion, we present novel experimental evidence that apoA-I enhances cardiac differentiation of ESCs and iPSCs and promotes maturation of the calcium handling property of ESC-derived cardiomyocytes via the BMP4/SMAD signaling pathway. © 2011 Ng et al.
Persistent Identifierhttp://hdl.handle.net/10722/134667
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
HKU201007176133
Sun Chieh Yeh Heart Foundation
Funding Information:

This work was supported by the HKU Small Project Funding (201007176133) to Kwong-Man Ng, Chung-Wah Siu and Hung-Fat Tse, and research funding from Sun Chieh Yeh Heart Foundation to Chung-Wah Siu. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorNg, KMen_HK
dc.contributor.authorLee, YKen_HK
dc.contributor.authorLai, WHen_HK
dc.contributor.authorChan, YCen_HK
dc.contributor.authorFung, MLen_HK
dc.contributor.authorTse, HFen_HK
dc.contributor.authorSiu, CWen_HK
dc.date.accessioned2011-07-05T08:23:54Z-
dc.date.available2011-07-05T08:23:54Z-
dc.date.issued2011en_HK
dc.identifier.citationPlos One, 2011, v. 6 n. 5en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/134667-
dc.description.abstractThe cardioprotective effects of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA-I) are well documented, but their effects in the direction of the cardiac differentiation of embryonic stem cells are unknown. We evaluated the effects of exogenous apoA-I expression on cardiac differentiation of ESCs and maturation of ESC-derived cardiomyocytes. We stably over-expressed full-length human apoA-I cDNA with lentivirus (LV)-mediated gene transfer in undifferentiated mouse ESCs and human induced pluripotent stem cells. Upon cardiac differentiation, we observed a significantly higher percentage of beating embryoid bodies, an increased number of cardiomyocytes as determined by flow cytometry, and expression of cardiac markers including α-myosin heavy chain, β-myosin heavy chain and myosin light chain 2 ventricular transcripts in LV-apoA-I transduced ESCs compared with control (LV-GFP). In the presence of noggin, a BMP4 antagonist, activation of BMP4-SMAD signaling cascade in apoA-I transduced ESCs completely abolished the apoA-I stimulated cardiac differentiation. Furthermore, co-application of recombinant apoA-I and BMP4 synergistically increased the percentage of beating EBs derived from untransduced D3 ESCs. These together suggests that that pro-cardiogenic apoA-I is mediated via the BMP4-SMAD signaling pathway. Functionally, cardiomyocytes derived from the apoA-I-transduced cells exhibited improved calcium handling properties in both non-caffeine and caffeine-induced calcium transient, suggesting that apoA-I plays a role in enhancing cardiac maturation. This increased cardiac differentiation and maturation has also been observed in human iPSCs, providing further evidence of the beneficial effects of apoA-I in promoting cardiac differentiation. In Conclusion, we present novel experimental evidence that apoA-I enhances cardiac differentiation of ESCs and iPSCs and promotes maturation of the calcium handling property of ESC-derived cardiomyocytes via the BMP4/SMAD signaling pathway. © 2011 Ng et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshApolipoprotein A-I - metabolism-
dc.subject.meshCalcium - metabolism-
dc.subject.meshCell Differentiation-
dc.subject.meshMyocardium - cytology - metabolism-
dc.subject.meshPluripotent Stem Cells - cytology-
dc.titleExogenous expression of human apoA-I enhances cardiac differentiation of pluripotent stem cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1932-6203&volume=6&issue=5, article no. e19787&spage=&epage=&date=2011&atitle=Exogenous+expression+of+human+apoA-I+enhances+cardiac+differentiation+of+pluripotent+stem+cells-
dc.identifier.emailNg, KM: skykmng@hkucc.hku.hken_HK
dc.identifier.emailChan, YC: ycchan09@hku.hken_HK
dc.identifier.emailFung, ML: fungml@hkucc.hku.hken_HK
dc.identifier.emailTse, HF: hftse@hkucc.hku.hken_HK
dc.identifier.emailSiu, CW: cwdsiu@hkucc.hku.hken_HK
dc.identifier.authorityNg, KM=rp01670en_HK
dc.identifier.authorityChan, YC=rp01502en_HK
dc.identifier.authorityFung, ML=rp00433en_HK
dc.identifier.authorityTse, HF=rp00428en_HK
dc.identifier.authoritySiu, CW=rp00534en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1371/journal.pone.0019787en_HK
dc.identifier.pmid21589943-
dc.identifier.pmcidPMC3092777-
dc.identifier.scopuseid_2-s2.0-79955884032en_HK
dc.identifier.hkuros202891-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79955884032&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue5en_HK
dc.identifier.isiWOS:000290483600030-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridNg, KM=25122990200en_HK
dc.identifier.scopusauthoridLee, YK=25958641200en_HK
dc.identifier.scopusauthoridLai, WH=18434390500en_HK
dc.identifier.scopusauthoridChan, YC=7403676116en_HK
dc.identifier.scopusauthoridFung, ML=7101955092en_HK
dc.identifier.scopusauthoridTse, HF=7006070805en_HK
dc.identifier.scopusauthoridSiu, CW=7006550690en_HK

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