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PMID:28262547
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| Citation |
Nishimura, K, Aizawa, S, Nugroho, FL, Shiomitsu, E, Tran, YT, Bui, PL, Borisova, E, Sakuragi, Y, Takada, H, Kurisaki, A, Hayashi, Y, Fukuda, A, Nakanishi, M and Hisatake, K (2017) A Role for KLF4 in Promoting the Metabolic Shift via TCL1 during Induced Pluripotent Stem Cell Generation. Stem Cell Reports 8:787-801 |
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| Abstract |
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. |
| Links |
PubMed Online version:10.1016/j.stemcr.2017.01.026 |
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