Molecular mechanism underlying miR-204-5p regulation of adipose-derived stem cells differentiation into cells from three germ layers

The limited differentiation ability of adipose-derived stem cells (ADSCs) limits their application in stem cell therapy and regenerative medicine. Here, we explore the molecular mechanism by which miR-204-5p regulates ADSCs differentiation into cells derived from the three germ layers (i.e., adipocytes, neurocytes, and hepatocytes). Although miR-204-5p overexpression inhibited ADSCs differentiation into adipocytes, neurocyte and hepatocyte differentiation were promoted. Mechanistically, miR-204-5p inhibited the expression of PPARG by regulating the AMPK signaling pathway, thereby inhibiting ADSCs differentiation into adipocytes. Further, miR-204-5p regulated JAG1/NOTCH3 axis for the inhibition of differentiation into adipocytes and promotion of differentiation into neurocytes. miR-204-5p might also promote ADSCs differentiation into hepatocytes by upregulating E2F8. The findings of this study provide novel insights into the regulatory mechanisms underlying early embryonic development and will help to facilitate the application of ADSCs in stem cell therapy and regenerative medicine.