CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes

Standard culture of human induced pluripotent stem cells (hiPSCs) requires basic Fibroblast Growth Factor (bFGF) to maintain the pluripotent state, whereas hiPSC more closely resemble epiblast stem cells than true naïve state ES which requires LIF to maintain pluripotency. Here we show that chemokin...

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Main Authors:	Hasegawa, Yuki, Tang, Dave, Takahashi, Naoko, Hayashizaki, Yoshihide, Forrest, Alistair R. R., the FANTOM consortium, Suzuki, Harukazu
Format:	Online
Language:	English
Published:	Nature Publishing Group 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067614/

id	pubmed-4067614
recordtype	oai_dc
spelling	pubmed-40676142014-06-24 CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes Hasegawa, Yuki Tang, Dave Takahashi, Naoko Hayashizaki, Yoshihide Forrest, Alistair R. R. the FANTOM consortium Suzuki, Harukazu Article Standard culture of human induced pluripotent stem cells (hiPSCs) requires basic Fibroblast Growth Factor (bFGF) to maintain the pluripotent state, whereas hiPSC more closely resemble epiblast stem cells than true naïve state ES which requires LIF to maintain pluripotency. Here we show that chemokine (C-C motif) ligand 2 (CCL2) enhances the expression of pluripotent marker genes through the phosphorylation of the signal transducer and activator of transcription 3 (STAT3) protein. Moreover, comparison of transcriptomes between hiPSCs cultured with CCL2 versus with bFGF, we found that CCL2 activates hypoxia related genes, suggesting that CCL2 enhanced pluripotency by inducing a hypoxic-like response. Further, we show that hiPSCs cultured with CCL2 can differentiate at a higher efficiency than culturing with just bFGF and we show CCL2 can be used in feeder-free conditions in the absence of LIF. Taken together, our finding indicates the novel functions of CCL2 in enhancing its pluripotency in hiPSCs. Nature Publishing Group 2014-06-24 /pmc/articles/PMC4067614/ /pubmed/24957798 http://dx.doi.org/10.1038/srep05228 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Hasegawa, Yuki Tang, Dave Takahashi, Naoko Hayashizaki, Yoshihide Forrest, Alistair R. R. the FANTOM consortium Suzuki, Harukazu
spellingShingle	Hasegawa, Yuki Tang, Dave Takahashi, Naoko Hayashizaki, Yoshihide Forrest, Alistair R. R. the FANTOM consortium Suzuki, Harukazu CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes
author_facet	Hasegawa, Yuki Tang, Dave Takahashi, Naoko Hayashizaki, Yoshihide Forrest, Alistair R. R. the FANTOM consortium Suzuki, Harukazu
author_sort	Hasegawa, Yuki
title	CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes
title_short	CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes
title_full	CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes
title_fullStr	CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes
title_full_unstemmed	CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes
title_sort	ccl2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes
description	Standard culture of human induced pluripotent stem cells (hiPSCs) requires basic Fibroblast Growth Factor (bFGF) to maintain the pluripotent state, whereas hiPSC more closely resemble epiblast stem cells than true naïve state ES which requires LIF to maintain pluripotency. Here we show that chemokine (C-C motif) ligand 2 (CCL2) enhances the expression of pluripotent marker genes through the phosphorylation of the signal transducer and activator of transcription 3 (STAT3) protein. Moreover, comparison of transcriptomes between hiPSCs cultured with CCL2 versus with bFGF, we found that CCL2 activates hypoxia related genes, suggesting that CCL2 enhanced pluripotency by inducing a hypoxic-like response. Further, we show that hiPSCs cultured with CCL2 can differentiate at a higher efficiency than culturing with just bFGF and we show CCL2 can be used in feeder-free conditions in the absence of LIF. Taken together, our finding indicates the novel functions of CCL2 in enhancing its pluripotency in hiPSCs.
publisher	Nature Publishing Group
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067614/
_version_	1612104997666816000

CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes

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