Generation of induced pluripotent stem cells (iPSCs) from somatic cells by deﬁned factors is a mechanism-unknown, yet extremely time-consuming process. Inefﬁcient reprogramming leads to prolonged periods of in vitro iPSC selection, resulting in subtle genetic and epigenetic abnormalities. To facilitate pluripotent reprogramming, we have identiﬁed the thyroid hormone triiodothyronine (T3) as an endogenous factor that can enhance reprogramming of human dermal ﬁbroblasts (HDF) and umbilical cord mesenchymal stem cells (UCMSC). This potentiation of iPSC induction is associated with metabolic remodeling activity, including upregulation of key glycolytic genes, an increase in cell proliferation, and the induction of mesenchymaleepithelial transition (MET). We further identify the activation of the PI3K/AKT signal pathway by T3 as an underlying mechanism for the enhanced conversion to cell pluripotency in this model. These studies demonstrate that T3 enhances metabolic remodeling of donor cells in potentiating cell reprogramming.
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