RRC ID 49491
Author Nishimura K, Aizawa S, Nugroho FL, Shiomitsu E, Tran YTH, Bui PL, Borisova E, Sakuragi Y, Takada H, Kurisaki A, Hayashi Y, Fukuda A, Nakanishi M, Hisatake K.
Title A Role for KLF4 in Promoting the Metabolic Shift via TCL1 during Induced Pluripotent Stem Cell Generation.
Journal Stem Cell Reports
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.
Volume 8(3)
Pages 787-801
Published 2017-3-14
DOI 10.1016/j.stemcr.2017.01.026
PII S2213-6711(17)30042-5
PMID 28262547
PMC PMC5355680
MeSH Animals Cellular Reprogramming* / genetics Energy Metabolism* Gene Expression Profiling Gene Expression Regulation Glycolysis Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / metabolism* Kruppel-Like Factor 4 Kruppel-Like Transcription Factors / genetics Kruppel-Like Transcription Factors / metabolism* Mice Mitochondria / genetics Mitochondria / metabolism Oxidative Phosphorylation Protein Binding Proto-Oncogene Proteins / metabolism* Proto-Oncogene Proteins c-akt / metabolism Signal Transduction
IF 6.032
Times Cited 10
DNA material B6N Mouse BAC clone (RDB07573): B6Ng01-102P12.
Human and Animal Cells Mouse iPSCs