title: CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes.
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.
authors: 1] Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho Tsurumi-ku Yokohama, Kanagawa, 230-0045 Japan [2] RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho Tsurumi-ku Yokohama, Kanagawa, 230-0045 Japan.
authors: Yuki
authors: Y
authors: Hasegawa
authors: 1] Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho Tsurumi-ku Yokohama, Kanagawa, 230-0045 Japan [2] RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho Tsurumi-ku Yokohama, Kanagawa, 230-0045 Japan.
authors: Dave
authors: D
authors: Tang
authors: 1] Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho Tsurumi-ku Yokohama, Kanagawa, 230-0045 Japan [2] RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho Tsurumi-ku Yokohama, Kanagawa, 230-0045 Japan.
authors: Naoko
authors: N
authors: Takahashi
authors: 1] Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho Tsurumi-ku Yokohama, Kanagawa, 230-0045 Japan [2] RIKEN Preventive Medicine and Diagnosis Innovation Program, 2-1 Hirosawa, Wako-shi, Saitama, 551-0198 Japan.
authors: Yoshihide
authors: Y
authors: Hayashizaki
authors: 1] Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho Tsurumi-ku Yokohama, Kanagawa, 230-0045 Japan [2] RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho Tsurumi-ku Yokohama, Kanagawa, 230-0045 Japan.
authors: Alistair R R
authors: AR
authors: Forrest
authors: 1] Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho Tsurumi-ku Yokohama, Kanagawa, 230-0045 Japan [2] RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho Tsurumi-ku Yokohama, Kanagawa, 230-0045 Japan.
authors: Harukazu
authors: H
authors: Suzuki
mesh_terms: D000475:Alkenes; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000494:pharmacology*; D002868:Chromosomal Proteins, Non-Histone; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects* / Q000378:metabolism; D053613:Janus Kinase 1; D053612:Janus Kinases / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071317:Nanog Homeobox Protein; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines; D039904:Pluripotent Stem Cells / Q000187:drug effects* / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D055746:Stage-Specific Embryonic Antigens / Q000378:metabolism
chemical_list: D000475:Alkenes; D018932:Chemokine CCL2; D002868:Chromosomal Proteins, Non-Histone; C466105:DPPA3 protein, human; D018398:Homeodomain Proteins; C121300:J 104129; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D010880:Piperidines; D011506:Proteins; D050796:STAT3 Transcription Factor; D055746:Stage-Specific Embryonic Antigens; C507976:ZFP42 protein, human; C066584:stage-specific embryonic antigen-4; D016222:Fibroblast Growth Factor 2; D053613:Janus Kinase 1; D053612:Janus Kinases