Journal Article A Role for KLF4 in Promoting the Metabolic Shift via TCL1 during Induced Pluripotent Stem Cell Generation

Nishimura, Ken  ,  Aizawa, Shiho  ,  Nugroho, Fransiska Liliani  ,  Shiomitsu, Emi  ,  Tran, Yen Thi Hai  ,  Bui, Phuong Linh  ,  Borisova, Evgeniia  ,  Sakuragi, Yuta  ,  Takada, Hitomi  ,  Kurisaki, Akira  ,  Hayashi, Yohei  ,  Fukuda, Aya  ,  Nakanishi, Mahito  ,  Hisatake, Koji

8 ( 3 )  , pp.787 - 801 , 2017-03 , Cell Press , Elsevier Inc.
Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is accompanied by morphological, functional, and metabolic alterations before acquisition of full pluripotency. Although the genome-wide effects of the reprogramming factors on gene expression are well documented, precise mechanisms by which gene expression changes evoke phenotypic responses remain to be determined. We used a Sendai virus-based system that permits reprogramming to progress in a strictly KLF4-dependent manner to screen for KLF4 target genes that are critical for the progression of reprogramming. The screening identified Tcl1 as a critical target gene that directs the metabolic shift from oxidative phosphorylation to glycolysis. KLF4-induced TCL1 employs a two-pronged mechanism, whereby TCL1 activates AKT to enhance glycolysis and counteracts PnPase to diminish oxidative phosphorylation. These regulatory mechanisms described here highlight a central role for a reprogramming factor in orchestrating the metabolic shift toward the acquisition of pluripotency during iPSC generation.

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