RRC ID 44219
Author Hasegawa Y, Tang D, Takahashi N, Hayashizaki Y, Forrest AR, FANTOM Consortium, Suzuki H.
Title CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes.
Journal Sci Rep
Abstract 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 withjust bFGF and we show CCL2 can be used in feeder-free conditions [corrected]. Taken together, our finding indicates the novel functions of CCL2 in enhancing its pluripotency in hiPSCs.
Volume 4
Pages 5228
Published 2014-6-24
DOI 10.1038/srep05228
PII srep05228
PMID 24957798
PMC PMC4067614
MeSH Alkenes Cell Differentiation / drug effects Cell Differentiation / genetics Cell Hypoxia / genetics Cells, Cultured Chemokine CCL2 / pharmacology* Chromosomal Proteins, Non-Histone Fibroblast Growth Factor 2 / pharmacology Gene Expression / drug effects* Homeodomain Proteins / genetics Homeodomain Proteins / metabolism Humans Immunoblotting Immunohistochemistry Induced Pluripotent Stem Cells / drug effects* Induced Pluripotent Stem Cells / metabolism Janus Kinase 1 Janus Kinases / metabolism Kruppel-Like Factor 4 Kruppel-Like Transcription Factors / genetics Kruppel-Like Transcription Factors / metabolism Nanog Homeobox Protein Phosphorylation / drug effects Piperidines Pluripotent Stem Cells / drug effects* Pluripotent Stem Cells / metabolism Proteins / genetics Proteins / metabolism Reverse Transcriptase Polymerase Chain Reaction STAT3 Transcription Factor / metabolism Signal Transduction / drug effects Stage-Specific Embryonic Antigens / metabolism
Resource
Human and Animal Cells 201B7(HPS0063)