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• W2012183860 abstract "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." @default.
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• W2012183860 date "2007-03-06" @default.
• W2012183860 modified "2023-10-17" @default.
• W2012183860 title "Mechanisms controlling the acquisition of a cardiac phenotype by liver stem cells" @default.
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• W2012183860 doi "https://doi.org/10.1073/pnas.0700416104" @default.
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