TY - JOUR
T1 - CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes
AU - Hasegawa, Yuki
AU - Tang, Dave
AU - Takahashi, Naoko
AU - Hayashizaki, Yoshihide
AU - Forrest, Alistair R. R.
AU - Suzuki, Harukazu
AU - AUTHOR GROUP
AU - Kawaji, Hideya
AU - Rehli, Michael
AU - Baillie, J. Kenneth
AU - de Hoon, Michiel J. L.
AU - Haberle, Vanja
AU - Lassmann, Timo
AU - Kulakovskiy, Ivan V.
AU - Lizio, Marina
AU - Itoh, Masayoshi
AU - Andersson, Robin
AU - Mungall, Christopher J.
AU - Meehan, Terrence F.
AU - Schmeier, Sebastian
AU - Bertin, Nicolas
AU - Jørgensen, Mette
AU - Dimont, Emmanuel
AU - Arner, Erik
AU - Schmidl, Christian
AU - Schaefer, Ulf
AU - Medvedeva, Yulia A.
AU - Plessy, Charles
AU - Vitezic, Morana
AU - Severin, Jessica
AU - Semple, Colin A.
AU - Ishizu, Yuri
AU - Young, Robert S.
AU - Francescatto, Margherita
AU - Alam, Intikhab
AU - Albanese, Davide
AU - Altschuler, Gabriel M.
AU - Arakawa, Takahiro
AU - Archer, John A. C.
AU - Arner, Peter
AU - Babina, Magda
AU - Baker, Sarah
AU - Balwierz, Piotr J.
AU - Beckhouse, Anthony G.
AU - Pradhan-Bhatt, Swati
AU - Blake, Judith A.
AU - Blumenthal, Antje
AU - Bodega, Beatrice
AU - Bonetti, Alessandro
AU - Briggs, James
AU - Geijtenbeek, Teunis B.
PY - 2014
Y1 - 2014
N2 - 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 naive 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
AB - 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 naive 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
U2 - https://doi.org/10.1038/srep05228
DO - https://doi.org/10.1038/srep05228
M3 - Article
C2 - 24957798
SN - 2045-2322
VL - 4
SP - 5228
JO - Scientific reports
JF - Scientific reports
ER -