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Article: Triiodothyronine promotes cardiac differentiation and maturation of embryonic stem cells via the classical genomic pathway

TitleTriiodothyronine promotes cardiac differentiation and maturation of embryonic stem cells via the classical genomic pathway
Authors
Issue Date2010
PublisherEndocrine Society. The Journal's web site is located at http://mend.endojournals.org/
Citation
Molecular Endocrinology, 2010, v. 24 n. 9, p. 1728-1736 How to Cite?
AbstractEmbryonic stem cells (ESCs) can differentiate into functional cardiomyocytes and thus represent a promising cell source for cardiac regenerative therapy. Nevertheless, the therapeutic application of ESC-derived cardiomyocytes is limited by the low efficacy of the current protocol for cardiac differentiation and their immature phenotypes. Although thyroid hormone is essential for normal cardiac development and function, its role in the cardiac differentiation of ESCs, as well as the maturation of ESC-derived cardiomyocytes, remains unclear. In this study, we examined the cardiac differentiation of murine ESCs in the presence of T3 for 7 d using flow cytometry, RT-PCR, cellular electrophysiology study, and confocal calcium imaging. Compared with control conditions, T3 supplementation increased the number of ESC-derived cardiomyocytes and was accompanied by up-regulation of a panel of cardiac markers, including Nkx2.5, myosin light chain-2V, as well as α- and β-myosin heavy chain. More importantly, electrophysiological study revealed that ESC-derived cardiomyocytes exhibited more adult-like phenotypes after T3 supplementation based on action potential characteristics. They also exhibited more adult-like calcium homeostasis properties. These phenotypic changes were associated with up-regulation of sarco(endo)plasmic reticulum calcium ATPase-2a and ryanodine receptor-2 expression. In addition, the classical (genomic) pathway was shown to be involved in T3-induced cardiac differentiation of ESCs. Our results show that T3 supplementation promotes cardiac differentiation of ESCs and enhances maturation of electrophysiological, as well as calcium homeostasis, properties of ESC-derived cardiomyocytes. Copyright © 2010 by The Endocrine Society.
Persistent Identifierhttp://hdl.handle.net/10722/65502
ISSN
2015 Impact Factor: 3.432
2015 SCImago Journal Rankings: 2.195
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grant CouncilHKU777910M
Funding Information:

Address all correspondence and requests for reprints to: Chung-Wah Siu, M.B.B.S., or H.-F. Tse, M.D., Ph.D., Cardiology Division, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China. E-mail: cwdsiu@hkucc.hku.hk; or E-mail: hftse@hkucc.hku.hk. This work was supported by the Hong Kong Research Grant Council (HKU777910M to Dr. Siu and Prof. Tse).

References

 

DC FieldValueLanguage
dc.contributor.authorLee, YKen_HK
dc.contributor.authorNg, KMen_HK
dc.contributor.authorChan, YCen_HK
dc.contributor.authorLai, WHen_HK
dc.contributor.authorAu, KWen_HK
dc.contributor.authorHo, CYJen_HK
dc.contributor.authorWong, LYen_HK
dc.contributor.authorLau, CPen_HK
dc.contributor.authorTse, HFen_HK
dc.contributor.authorSiu, CWen_HK
dc.date.accessioned2010-08-24T01:51:48Z-
dc.date.available2010-08-24T01:51:48Z-
dc.date.issued2010en_HK
dc.identifier.citationMolecular Endocrinology, 2010, v. 24 n. 9, p. 1728-1736en_HK
dc.identifier.issn0888-8809en_HK
dc.identifier.urihttp://hdl.handle.net/10722/65502-
dc.description.abstractEmbryonic stem cells (ESCs) can differentiate into functional cardiomyocytes and thus represent a promising cell source for cardiac regenerative therapy. Nevertheless, the therapeutic application of ESC-derived cardiomyocytes is limited by the low efficacy of the current protocol for cardiac differentiation and their immature phenotypes. Although thyroid hormone is essential for normal cardiac development and function, its role in the cardiac differentiation of ESCs, as well as the maturation of ESC-derived cardiomyocytes, remains unclear. In this study, we examined the cardiac differentiation of murine ESCs in the presence of T3 for 7 d using flow cytometry, RT-PCR, cellular electrophysiology study, and confocal calcium imaging. Compared with control conditions, T3 supplementation increased the number of ESC-derived cardiomyocytes and was accompanied by up-regulation of a panel of cardiac markers, including Nkx2.5, myosin light chain-2V, as well as α- and β-myosin heavy chain. More importantly, electrophysiological study revealed that ESC-derived cardiomyocytes exhibited more adult-like phenotypes after T3 supplementation based on action potential characteristics. They also exhibited more adult-like calcium homeostasis properties. These phenotypic changes were associated with up-regulation of sarco(endo)plasmic reticulum calcium ATPase-2a and ryanodine receptor-2 expression. In addition, the classical (genomic) pathway was shown to be involved in T3-induced cardiac differentiation of ESCs. Our results show that T3 supplementation promotes cardiac differentiation of ESCs and enhances maturation of electrophysiological, as well as calcium homeostasis, properties of ESC-derived cardiomyocytes. Copyright © 2010 by The Endocrine Society.en_HK
dc.languageeng-
dc.publisherEndocrine Society. The Journal's web site is located at http://mend.endojournals.org/en_HK
dc.relation.ispartofMolecular Endocrinologyen_HK
dc.subject.meshCell Differentiation - drug effects-
dc.subject.meshEmbryonic Stem Cells - cytology - drug effects - metabolism-
dc.subject.meshGenome - genetics-
dc.subject.meshMyocardium - cytology - metabolism-
dc.subject.meshTriiodothyronine - pharmacology-
dc.titleTriiodothyronine promotes cardiac differentiation and maturation of embryonic stem cells via the classical genomic pathwayen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0888-8809&volume=24&issue=9&spage=1728&epage=1736&date=2010&atitle=Triiodothyronine+promotes+cardiac+differentiation+and+maturation+of+embryonic+stem+cells+via+the+classical+genomic+pathway-
dc.identifier.emailChan, YC:yauchi@graduate.hku.hken_HK
dc.identifier.emailTse, HF:hftse@hkucc.hku.hken_HK
dc.identifier.emailSiu, CW:cwdsiu@hkucc.hku.hken_HK
dc.identifier.authorityChan, YC=rp01502en_HK
dc.identifier.authorityTse, HF=rp00428en_HK
dc.identifier.authoritySiu, CW=rp00534en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1210/me.2010-0032en_HK
dc.identifier.pmid20667986-
dc.identifier.scopuseid_2-s2.0-77956127107en_HK
dc.identifier.hkuros174012-
dc.identifier.hkuros200910-
dc.identifier.hkuros169708-
dc.identifier.hkuros169710-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77956127107&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume24en_HK
dc.identifier.issue9en_HK
dc.identifier.spage1728en_HK
dc.identifier.epage1736en_HK
dc.identifier.isiWOS:000281387300004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLee, YK=25958641200en_HK
dc.identifier.scopusauthoridNg, KM=25122990200en_HK
dc.identifier.scopusauthoridChan, YC=7403676116en_HK
dc.identifier.scopusauthoridLai, WH=18434390500en_HK
dc.identifier.scopusauthoridAu, KW=9738204200en_HK
dc.identifier.scopusauthoridHo, CYJ=37026220200en_HK
dc.identifier.scopusauthoridWong, LY=36097267000en_HK
dc.identifier.scopusauthoridLau, CP=7401968501en_HK
dc.identifier.scopusauthoridTse, HF=7006070805en_HK
dc.identifier.scopusauthoridSiu, CW=7006550690en_HK

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