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Article: Absence of transverse tubules contributes to non-uniform Ca2+ wavefronts in mouse and human embryonic stem cell-derived cardiomyocytes

TitleAbsence of transverse tubules contributes to non-uniform Ca2+ wavefronts in mouse and human embryonic stem cell-derived cardiomyocytes
Authors
Issue Date2009
PublisherMary Ann Liebert, Inc Publishers. The Journal's web site is located at http://www.liebertpub.com/jht
Citation
Stem Cells And Development, 2009, v. 18 n. 10, p. 1493-1500 How to Cite?
AbstractMouse (m) and human embryonic stem cell-derived cardiomyocytes (hESC-CMs) are known to exhibit immature Ca2+ dynamics such as small whole-cell peak amplitude and slower kinetics relative to those of adult. In this study, we examined the maturity and efficiency of Ca2+-induced Ca2+ release in m and hESC-CMs, the presence of transverse (t) tubules and its effects on the regional Ca2+ dynamics. In m and hESC-CMs, fluorescent staining and atomic force microscopy (AFM) were used to detect the presence of t-tubules, caveolin-3, amphiphysin-2 and colocalization of dihydropyridine receptors (DHPRs) and ryanodine receptors (RyRs). To avoid ambiguities, regional electrically-stimulated Ca2+ dynamics of single ESC-CMs, rather than spontaneously beating clusters, were measured using confocal microscopy. m and hESC-CMs showed absence of dyads, with neither t-tubules nor colocalization of DHPRs and RyRs. Caveolin-3 and amphiphysin-2, crucial for the biogenesis of t-tubules with robust expression in adult CMs, were also absent. Single m and hESC-CMs displayed non-uniform Ca2+ dynamics across the cell that is typical of CMs deficient of t-tubules. Local Ca2+ transients exhibited greater peak amplitude at the peripheral than at the central region for m (3.50 ± 0.42 vs. 3.05 ± 0.38) and hESC-CMs (2.96 ± 0.25 vs. 2.72 ± 0.25). Kinetically, both the rates of rise to peak amplitude and transient decay were faster for the peripheral relative to the central region. Immature m and hESC-CMs display unsynchronized Ca2+ transients due to the absence of t-tubules and gene products crucial for their biogenesis. Our results provide insights for driving the maturation of ESC-CMs. © 2009 Mary Ann Liebert, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/59249
ISSN
2015 Impact Factor: 3.777
2015 SCImago Journal Rankings: 1.703
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Institutes of HealthR01-HL72857
California Institute of Regenerative Medicine
Stem Cell Program of the University of California, Davis
Research Grant Council
CC Wong Stem Cell Fund
NSF Center for Biophotonics Science Technology
Shriners Hospital for Children
NSF Science and Technology CenterPHY 0120999
Croucher Fellowship5TL1RR024145-02
Funding Information:

This work was supported by the National Institutes of Health (R01-HL72857 to R. A. L.), the California Institute of Regenerative Medicine (to R. A. L.), the Stem Cell Program of the University of California, Davis (to R. A. L.), and Research Grant Council and CC Wong Stem Cell Fund (to R. A. L. and H. F. T.). D. K. L. was supported by a fellowship from the NSF Center for Biophotonics Science & Technology and a fellowship from Shriners Hospital for Children. The Center for Biophotonics, an NSF Science and Technology Center, is managed by the University of California, Davis, under Cooperative Agreement No. PHY 0120999. C. W. S. and A. A. K. were supported by a Croucher Fellowship and a T32 training grant (5TL1RR024145-02), respectively, during the tenure of this project.

References

 

DC FieldValueLanguage
dc.contributor.authorLieu, DKen_HK
dc.contributor.authorLiu, Jen_HK
dc.contributor.authorSiu, CWen_HK
dc.contributor.authorMcNerney, GPen_HK
dc.contributor.authorTse, HFen_HK
dc.contributor.authorAbu-Khalil, Aen_HK
dc.contributor.authorHuser, Ten_HK
dc.contributor.authorLi, RAen_HK
dc.date.accessioned2010-05-31T03:46:09Z-
dc.date.available2010-05-31T03:46:09Z-
dc.date.issued2009en_HK
dc.identifier.citationStem Cells And Development, 2009, v. 18 n. 10, p. 1493-1500en_HK
dc.identifier.issn1547-3287en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59249-
dc.description.abstractMouse (m) and human embryonic stem cell-derived cardiomyocytes (hESC-CMs) are known to exhibit immature Ca2+ dynamics such as small whole-cell peak amplitude and slower kinetics relative to those of adult. In this study, we examined the maturity and efficiency of Ca2+-induced Ca2+ release in m and hESC-CMs, the presence of transverse (t) tubules and its effects on the regional Ca2+ dynamics. In m and hESC-CMs, fluorescent staining and atomic force microscopy (AFM) were used to detect the presence of t-tubules, caveolin-3, amphiphysin-2 and colocalization of dihydropyridine receptors (DHPRs) and ryanodine receptors (RyRs). To avoid ambiguities, regional electrically-stimulated Ca2+ dynamics of single ESC-CMs, rather than spontaneously beating clusters, were measured using confocal microscopy. m and hESC-CMs showed absence of dyads, with neither t-tubules nor colocalization of DHPRs and RyRs. Caveolin-3 and amphiphysin-2, crucial for the biogenesis of t-tubules with robust expression in adult CMs, were also absent. Single m and hESC-CMs displayed non-uniform Ca2+ dynamics across the cell that is typical of CMs deficient of t-tubules. Local Ca2+ transients exhibited greater peak amplitude at the peripheral than at the central region for m (3.50 ± 0.42 vs. 3.05 ± 0.38) and hESC-CMs (2.96 ± 0.25 vs. 2.72 ± 0.25). Kinetically, both the rates of rise to peak amplitude and transient decay were faster for the peripheral relative to the central region. Immature m and hESC-CMs display unsynchronized Ca2+ transients due to the absence of t-tubules and gene products crucial for their biogenesis. Our results provide insights for driving the maturation of ESC-CMs. © 2009 Mary Ann Liebert, Inc.en_HK
dc.languageengen_HK
dc.publisherMary Ann Liebert, Inc Publishers. The Journal's web site is located at http://www.liebertpub.com/jhten_HK
dc.relation.ispartofStem Cells and Developmenten_HK
dc.rightsThis is a copy of an article published in the Stem Cells and Development © 2009 copyright Mary Ann Liebert, Inc.; Stem Cells and Development is available online at: http://www.liebertonline.com-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAnimalsen_HK
dc.subject.meshCalcium Channels, L-Type - metabolismen_HK
dc.subject.meshCalcium Signalingen_HK
dc.subject.meshCaveolin 3 - metabolismen_HK
dc.subject.meshElectric Stimulationen_HK
dc.subject.meshEmbryonic Stem Cells - cytology - metabolismen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMyocytes, Cardiac - cytology - metabolismen_HK
dc.subject.meshNerve Tissue Proteins - metabolismen_HK
dc.subject.meshProtein Transporten_HK
dc.subject.meshRyanodine Receptor Calcium Release Channel - metabolismen_HK
dc.titleAbsence of transverse tubules contributes to non-uniform Ca2+ wavefronts in mouse and human embryonic stem cell-derived cardiomyocytesen_HK
dc.typeArticleen_HK
dc.identifier.emailSiu, CW:cwdsiu@hkucc.hku.hken_HK
dc.identifier.emailTse, HF:hftse@hkucc.hku.hken_HK
dc.identifier.emailLi, RA:ronaldli@hkucc.hku.hken_HK
dc.identifier.authoritySiu, CW=rp00534en_HK
dc.identifier.authorityTse, HF=rp00428en_HK
dc.identifier.authorityLi, RA=rp01352en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1089/scd.2009.0052en_HK
dc.identifier.pmid19290776-
dc.identifier.pmcidPMC3139544-
dc.identifier.scopuseid_2-s2.0-67650022307en_HK
dc.identifier.hkuros158859en_HK
dc.identifier.hkuros182838-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67650022307&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume18en_HK
dc.identifier.issue10en_HK
dc.identifier.spage1493en_HK
dc.identifier.epage1500en_HK
dc.identifier.isiWOS:000272591600013-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLieu, DK=7003924538en_HK
dc.identifier.scopusauthoridLiu, J=8429607500en_HK
dc.identifier.scopusauthoridSiu, CW=7006550690en_HK
dc.identifier.scopusauthoridMcNerney, GP=23088712000en_HK
dc.identifier.scopusauthoridTse, HF=7006070805en_HK
dc.identifier.scopusauthoridAbuKhalil, A=6507993743en_HK
dc.identifier.scopusauthoridHuser, T=7004227222en_HK
dc.identifier.scopusauthoridLi, RA=7404724466en_HK
dc.customcontrol.immutablejt 130822-

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