CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes
Yuki Hasegawa, Dave Tang, Naoko Takahashi, Yoshihide Hayashizaki, Alistair RR Forrest, Harukazu Suzuki
Scientific Reports | NATURE PUBLISHING GROUP | Published : 2014
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 re..View full abstract
Awarded by European Union
Awarded by EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
Awarded by NATIONAL CANCER INSTITUTE
We are grateful to S. Yamanaka and K. Takahashi in CiRA for sharing their knowledge on how to establish and handle induced pluripotent stem cells. We also greatly appreciate to S. Koseki and D. Yamada for sharing multiple human iPS cell lines. We are thankful to H. Mori in Protein Crystal. LTD for providing CCL2 protein beads and sharing his knowledge and technology. We also greatly appreciate T. Suzuki's technical supports. This work was supported in part by grant for FS stage A-STEP (Adaptable & Seamless Technology Transfer Program through Target-driven R&D) by JST to Y. Hasegawa. FANTOM5 was made possible by a Research Grant for RIKEN Omics Science Center from MEXT to Y. Hayashizaki a Grant of the Innovative Cell Biology by Innovative Technology (Cell Innovation Program) from the MEXT, Japan to Y. Hayashizaki and to the RIKEN Center for Life Science Technologies. We would like to thank all members of the FANTOM5 consortium for the contribution of samples and analysis of the data-set and thank GeNAS for the data production. D. T. is supported by The European Union Seventh Framework Programme under grant agreement [FP7-People-ITN-2008-238055] ('BrainTrain' project).