Reference - Detail
RRC ID | 49491 |
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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 |
Resource | |
DNA material | B6N Mouse BAC clone (RDB07573): B6Ng01-102P12. |
Human and Animal Cells | Mouse iPSCs |