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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2010-6-23
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pubmed:abstractText |
Various types of cardiomyocytes undergo changes in automaticity and electrical properties during fetal heart development. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs), like fetal cardiomyocytes, are electrophysiologically immature and exhibit automaticity. We used hESC-CMs to investigate developmental changes in mechanisms of automaticity and to determine whether electrophysiological maturation is driven by an intrinsic developmental clock and/or is regulated by interactions with non-cardiomyocytes in embryoid bodies (EBs). We isolated pure populations of hESC-CMs from EBs by lentivirus-engineered Puromycin resistance at various stages of differentiation. Using pharmacological agents, calcium (Ca(2+)) imaging, and intracellular recording techniques, we found that intracellular Ca(2+)-cycling mechanisms developed early and contributed to dominant automaticity throughout hESC-CM differentiation. Sarcolemmal ion channels evolved later upon further differentiation within EBs and played an increasing role in controlling automaticity and electrophysiological properties of hESC-CMs. In contrast to the development of intracellular Ca(2+)-handling proteins, ion channel development and electrophysiological maturation of hESC-CMs did not occur when hESC-CMs were isolated from EBs early and maintained in culture without further interaction with non-cardiomyocytes. Adding back non-cardiomyocytes to early-isolated hESC-CMs rescued the arrest of electrophysiological maturation, indicating that non-cardiomyocytes in EBs drive electrophysiological maturation of early hESC-CMs. Non-cardiomyocytes in EBs contain most cell types present in the embryonic heart that are known to influence early cardiac development. Our study is the first to demonstrate that non-cardiomyocytes influence electrophysiological maturation of early hESC-CMs in cultures. Defining the nature of these extrinsic signals will aid in the directed maturation of immature hESC-CMs to mitigate arrhythmogenic risks of cell-based therapies.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-10600869,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-11249878,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-12169644,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-1266712,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-12742992,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-12791707,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-15243138,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-15385154,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-15448703,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-15758029,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-15979127,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-16322641,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-16990699,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-17132784,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-17255522,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-17379641,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-17420362,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-17435178,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-17459410,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-17656646,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-17872499,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-18071321,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-18375593,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-18483424,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-18534373,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-19352491,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-2447944,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-7528293,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-7864010,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-8603498,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20001453-9777731
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic Nucleotide-Gated Cation...,
http://linkedlifedata.com/resource/pubmed/chemical/HCN4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/ICI D2788,
http://linkedlifedata.com/resource/pubmed/chemical/Muscle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Puromycin,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrodotoxin
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1557-8534
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
783-95
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
pubmed-meshheading:20001453-Action Potentials,
pubmed-meshheading:20001453-Calcium Signaling,
pubmed-meshheading:20001453-Cell Differentiation,
pubmed-meshheading:20001453-Cell Line,
pubmed-meshheading:20001453-Cyclic Nucleotide-Gated Cation Channels,
pubmed-meshheading:20001453-Electrophysiological Phenomena,
pubmed-meshheading:20001453-Embryo, Mammalian,
pubmed-meshheading:20001453-Embryonic Stem Cells,
pubmed-meshheading:20001453-Gene Expression Regulation, Developmental,
pubmed-meshheading:20001453-Humans,
pubmed-meshheading:20001453-Intracellular Space,
pubmed-meshheading:20001453-Ion Channel Gating,
pubmed-meshheading:20001453-Muscle Proteins,
pubmed-meshheading:20001453-Myocytes, Cardiac,
pubmed-meshheading:20001453-Puromycin,
pubmed-meshheading:20001453-Pyrimidines,
pubmed-meshheading:20001453-RNA, Messenger,
pubmed-meshheading:20001453-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20001453-Sodium Channels,
pubmed-meshheading:20001453-Spheroids, Cellular,
pubmed-meshheading:20001453-Tetrodotoxin
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pubmed:year |
2010
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pubmed:articleTitle |
Non-cardiomyocytes influence the electrophysiological maturation of human embryonic stem cell-derived cardiomyocytes during differentiation.
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pubmed:affiliation |
Center for Neuroscience, Aging and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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