Promotion of the induction of cell pluripotency through metabolic remodeling by thyroid hormone triiodothyronine-activated PI3K/AKT signal pathway.

Biomaterials
Mengfei ChenTao Li

Abstract

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 mesenchymal-epithelial 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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Citations

Nov 26, 2015·Molecular Diagnosis & Therapy·Zahra Nozhat, Mehdi Hedayati
Aug 28, 2015·Journal of Cellular Biochemistry·Xiangqing ZhuJi-Fan Hu
Mar 26, 2013·Stem Cells·Myung Jin SonYee Sook Cho
Oct 10, 2013·International Journal of Cancer. Journal International Du Cancer·Shenghong ZhangJifan Hu
Oct 8, 2013·Experimental Cell Research·Omer HabibHyung-Min Chung
Nov 27, 2014·World Journal of Stem Cells·Kate HawkinsTristan McKay
Nov 13, 2020·PloS One·Elena A OstrakhovitchSiamak Tabibzadeh
May 31, 2021·Journal of Cellular and Molecular Medicine·Shan HuangLu Cai

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