Mechanisms controlling the acquisition of a cardiac phenotype by liver stem cells
| Autor: | William B. Coleman, Barbara J. Muller-Borer, Page A.W. Anderson, Hyung Suk Kim, Nadia N. Malouf, Joe W. Grisham, Wayne E. Cascio, Gwyn L. Esch |
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| Rok vydání: | 2007 |
| Předmět: |
Cytoplasm
Cellular differentiation Cell Liver Stem Cell Connexin Biology digestive system Rats Sprague-Dawley medicine Animals Receptor Cell Nucleus Multidisciplinary Myocardium Stem Cells Gap Junctions Nuclear Proteins Cell Differentiation Biological Sciences respiratory system digestive system diseases Rats Inbred F344 Rats Cell biology Cell nucleus surgical procedures operative Phenotype medicine.anatomical_structure Liver Myocardin Connexin 43 cardiovascular system Trans-Activators Calcium Stem cell |
| Zdroj: | Proceedings of the National Academy of Sciences. 104:3877-3882 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0700416104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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