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

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 mec...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355680/
https://www.ncbi.nlm.nih.gov/pubmed/28262547
http://dx.doi.org/10.1016/j.stemcr.2017.01.026
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author 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
author_facet 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
author_sort Nishimura, Ken
collection PubMed
description 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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spelling pubmed-53556802017-03-24 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 Stem Cell Reports Article 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. Elsevier 2017-03-02 /pmc/articles/PMC5355680/ /pubmed/28262547 http://dx.doi.org/10.1016/j.stemcr.2017.01.026 Text en © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
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
A Role for KLF4 in Promoting the Metabolic Shift via TCL1 during Induced Pluripotent Stem Cell Generation
title A Role for KLF4 in Promoting the Metabolic Shift via TCL1 during Induced Pluripotent Stem Cell Generation
title_full A Role for KLF4 in Promoting the Metabolic Shift via TCL1 during Induced Pluripotent Stem Cell Generation
title_fullStr A Role for KLF4 in Promoting the Metabolic Shift via TCL1 during Induced Pluripotent Stem Cell Generation
title_full_unstemmed A Role for KLF4 in Promoting the Metabolic Shift via TCL1 during Induced Pluripotent Stem Cell Generation
title_short A Role for KLF4 in Promoting the Metabolic Shift via TCL1 during Induced Pluripotent Stem Cell Generation
title_sort role for klf4 in promoting the metabolic shift via tcl1 during induced pluripotent stem cell generation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355680/
https://www.ncbi.nlm.nih.gov/pubmed/28262547
http://dx.doi.org/10.1016/j.stemcr.2017.01.026
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