Document Detail

Mechanisms controlling the acquisition of a cardiac phenotype by liver stem cells.
MedLine Citation:
PMID:  17360446     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-02-26
Journal Detail:
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:
Created Date:  2007-03-15     Completed Date:  2007-04-24     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3877-82     Citation Subset:  IM    
Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
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MeSH Terms
Calcium / metabolism*
Cell Differentiation
Cell Nucleus / metabolism
Connexin 43 / biosynthesis
Cytoplasm / metabolism
Gap Junctions
Liver / cytology*
Myocardium / metabolism*
Nuclear Proteins / biosynthesis
Rats, Inbred F344
Rats, Sprague-Dawley
Stem Cells / cytology*
Trans-Activators / biosynthesis
Grant Support
Reg. No./Substance:
0/Connexin 43; 0/Nuclear Proteins; 0/Trans-Activators; 0/myocardin; 7440-70-2/Calcium

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