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CCL2 Enhances Pluripotency of Human Induced Pluripotent Stem Cells by Activating Hypoxia Related Genes

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Journal Sci Rep
Specialty Science
Date 2014 Jun 25
PMID 24957798
Citations 11
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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.

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References
1.
Fan G, Tran J . X chromosome inactivation in human and mouse pluripotent stem cells. Hum Genet. 2011; 130(2):217-22. PMC: 3965368. DOI: 10.1007/s00439-011-1038-1. View

2.
Tsuchihara K, Suzuki Y, Wakaguri H, Irie T, Tanimoto K, Hashimoto S . Massive transcriptional start site analysis of human genes in hypoxia cells. Nucleic Acids Res. 2009; 37(7):2249-63. PMC: 2673422. DOI: 10.1093/nar/gkp066. View

3.
Hasegawa Y, Takahashi N, Forrest A, Shin J, Kinoshita Y, Suzuki H . CC chemokine ligand 2 and leukemia inhibitory factor cooperatively promote pluripotency in mouse induced pluripotent cells. Stem Cells. 2011; 29(8):1196-205. DOI: 10.1002/stem.673. View

4.
James D, Levine A, Besser D, Hemmati-Brivanlou A . TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells. Development. 2005; 132(6):1273-82. DOI: 10.1242/dev.01706. View

5.
Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-76. DOI: 10.1016/j.cell.2006.07.024. View