Transient epigenetic changes promote cardiomyocyte differentiation of the subcutaneous adipose stromal vascular fraction.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Introduction The subcutaneous adipose-tissue-derived stromal vascular fraction (Sa-SVF) contains stem/progenitor cells that rarely transdifferentiate into beating cardiomyocytes. Previously, we developed a culture protocol in which adult murine inguinal Sa-SVF cells reproducibly transdifferentiate into beating cardiomyocyte-like cells (beating CMs) without any specific induction in the primary culture. However, the mechanism underlying the differentiation of the Sa-SVF toward the cardiac lineage is unclear. Methods To identify a key regulator of cardiac differentiation, we investigated sequential changes in global gene expression profiles of Sa-SVF cells during primary culture. Sa-SVF cells were isolated from adult murine inguinal subcutaneous fat pads and cultured using our beating CM induction method. At six time points during primary culture, total RNA was extracted and subjected to RNA-sequencing and quantitative polymerase chain reaction analysis. Results Beating CMs appeared on day 14. Of 14,574 prefiltered genes, 749 showed significant expression changes (153 upregulated and 596 downregulated, > 2-fold) between days 7 and 14, coinciding with the appearance of beating CMs. Gene ontology analysis highlighted histone deacetylase (HDAC)-associated genes, expression of which was transiently suppressed during the period when cardiac sarcomere-related genes and the transcriptio

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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