Myogenic differentiation in atrium‐derived adult cardiac pluripotent cells and the transcriptional regulation of GATA4 and myogenin on ANP promoter

Abstract

We established cardiac pluripotent stem-like cells from the left atrium (LA-PCs) of adult rat hearts. These cells could differentiate not only into beating myocytes but also into cells of other lineages, including adipocytes and endothelial cells in the methylcellulose-based medium containing interleukin-3 (IL-3), interleukin-6 (IL-6), and stem cell factor (SCF). In particular, IL-3 and SCF contributed to the differentiation into cardiac troponin I-positive cells. Notably, small population of LA-PCs coexpressed GATA4 and myogenin, which are markers specific to cardiomyocytes and skeletal myocytes, respectively, and could differentiate into both cardiac and skeletal myocytes. Therefore, we investigated the involvement of these two tissue-specific transcription factors in the cardiac transcriptional activity. Coexpression of GATA4 and myogenin synergistically activated GATA4-specific promoter of the atrial natriuretic peptide gene. This combinatorial function was shown to be dependant on the GATA site, but independent of the E-box. The results of chromatin immunoprecipitation and electrophoretic mobility shift assays suggested that myogenin bound to GATA4 on the GATA elements and the C-terminal Zn-finger domain of GATA4 and the N-terminal region of myogenin were required for this synergistic activation of transcription. Taken together, these two transcription factors could be involved in the myogenesis of LA-PCs.

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“…The study also demonstrated spontaneous differentiation into skeletal myocytes [100]. Hasan et al [101] established cardiac pluripotent stem cell‐like cells from the left atrium of adult rat hearts that could differentiate into beating cardiomyocytes in the methylcellulose‐based medium containing interleukin‐3 and stem cell factor, which contributed to the differentiation into cardiac troponin I‐positive cells. Distinctly small populations of pluripotent stem cell‐like cells from the left atrium coexpressed GATA4 and myogenin, which are markers specific to cardiomyocytes and skeletal myocytes, respectively.…”

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“…The amount of GATA-4 mRNA expression drifts at different passages of the bulk culture lots [15]. However, when the source of c-kit pos CSCs is limited to the left atrium, a higher proportion of bulk cultures exhibited markers for cardiac lineage and some produced beating cells when placed into differentiation media with cytokines Il-3 and SCF [18]. The bulk cultures were subjected to cloning by limited dilution methods, and the characteristics of clones obtained were not perfectly identical to the original bulk culture, perhaps due to heterogeneity within the bulk culture cells [15, 17, 18].…”

Cancer research by means of tissue engineering – is there a rationale?

“…Cardiac infarction has been of special interest with regard to regeneration because of the vital consequences of functional loss when myocardial tissue is lost. Molecular analysis of cardiac stem cells for cardiac regeneration is believed to be instrumental to establish cardiac regeneration technologies . Researchers have investigated the close relationship between telocytes and cardiac stem cells.…”