| Mechanisms controlling the acquisition of a cardiac phenotype by liver stem cells. | |
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MedLine Citation:
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PMID: 17360446 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mechanisms underlying stem cell acquisition of a cardiac phenotype are unresolved. We studied early events during the acquisition of a cardiac phenotype by a cloned adult liver stem cell line (WB F344) in a cardiac microenvironment. WB F344 cells express a priori the transcription factors GATA4 and SRF, connexin 43 in the cell membrane, and myoinositol 1,4,5-triphosphate receptor in the perinuclear region. Functional cell-cell communication developed between WB F344 cells and adjacent cocultured cardiomyocytes in 24 h. De novo cytoplasmic [Ca(2+)](c) and nuclear [Ca(2+)](nu) oscillations appeared in WB F344 cells, synchronous with [Ca(2+)](i) transients in adjacent cardiomyocytes. The [Ca(2+)] oscillations in the WB F344 cells, but not those in the cardiomyocytes, were eliminated by a gap junction uncoupler and reappeared with its removal. By 24 h, WB F344 cells began expressing the cardiac transcription factors Nkx2.5, Tbx5, and cofactor myocardin; cardiac proteins 24 h later; and a sarcomeric pattern 4-6 days later. Myoinositol 1,4,5-triphosphate receptor inhibition suppressed WB F344 cell [Ca(2+)](nu) oscillations but not [Ca(2+)](c) oscillations, and L-type calcium channel inhibition eliminated [Ca(2+)] oscillations in cardiomyocytes and WB F344 cells. The use of these inhibitors was associated with a decrease in Nkx2.5, Tbx5, and myocardin expression in the WB F344 cells. Our findings suggest that signals from cardiomyocytes diffuse through shared channels, inducing [Ca(2+)] oscillations in the WB F344 cells. We hypothesize that the WB F344 cell [Ca(2+)](nu) oscillations activate the expression of a cardiac specifying gene program, ushering in a cardiac phenotype. |
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Authors:
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Barbara J Muller-Borer; Wayne E Cascio; Gwyn L Esch; Hyung-Suk Kim; William B Coleman; Joe W Grisham; Page A W Anderson; Nadia N Malouf |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2007-02-26 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 104 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2007 Mar |
Date Detail:
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Created Date: 2007-03-15 Completed Date: 2007-04-24 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 3877-82 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium / metabolism* Cell Differentiation Cell Nucleus / metabolism Connexin 43 / biosynthesis Cytoplasm / metabolism Gap Junctions Liver / cytology* Myocardium / metabolism* Nuclear Proteins / biosynthesis Phenotype Rats Rats, Inbred F344 Rats, Sprague-Dawley Stem Cells / cytology* Trans-Activators / biosynthesis |
| Grant Support | |
ID/Acronym/Agency:
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HL 67385/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Connexin 43; 0/Nuclear Proteins; 0/Trans-Activators; 0/myocardin; 7440-70-2/Calcium |
| Comments/Corrections | |
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