title: Promotion of the induction of cell pluripotency through metabolic remodeling by thyroid hormone triiodothyronine-activated PI3K/AKT signal pathway.
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.
authors.affiliation: Shenzhen Beike Cell Engineering Research Institute, Yuanxing Science and Technology Building, Nanshan, Shenzhen, China.
authors.forename: Mengfei
authors.initials: M
authors.lastname: Chen
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.forename: Di
authors.initials: D
authors.lastname: Xu
authors.forename: Jingnan
authors.initials: J
authors.lastname: Sun
authors.forename: Yixin
authors.initials: Y
authors.lastname: He
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Zhaojing
authors.initials: Z
authors.lastname: Wang
authors.forename: Lifang
authors.initials: L
authors.lastname: Wu
authors.forename: Shaokun
authors.initials: S
authors.lastname: Xu
authors.forename: Jinsong
authors.initials: J
authors.lastname: Wang
authors.forename: Shu
authors.initials: S
authors.lastname: Jiang
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Zhou
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hoffman
authors.forename: Xiang
authors.initials: X
authors.lastname: Hu
authors.forename: Jifan
authors.initials: J
authors.lastname: Hu
authors.forename: Tao
authors.initials: T
authors.lastname: Li
mesh_terms: D000328:Adult; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D014284:Triiodothyronine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt