1. CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes
- Author
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Hasegawa, Y., Tang, D., Takahashi, N., Hayashizaki, Y., Forrest, A.R.R., Hideya, K., Michael, R., J Kenneth Baillie, Michiel J, L.D.H., Vanja, H., Timo, L., Ivan, V.K., Marina, L., Masayoshi, I., Robin, A., Christopher, J.M., Terrence, F.M., Sebastian, S., Nicolas, B., Mette, J., Emmanuel, D., Erik, A., Christian, S., Ulf, S., Yulia, A.M., Charles, P., Morana, V., Jessica, S., Colin, A.S., Yuri, I., Robert, S.Y., Margherita, F., Intikhab, A., Davide, A., Gabriel, M.A., Takahiro, A., John A, C.A., Peter, A., Magda, B., Sarah, B., Piotr, J.B., Anthony, G.B., Swati, P., Judith, A.B., Antje, B., Bodega, B., Alessandro, B., James, B., Frank, B., A Maxwell Burroughs, Andrea, C., Carlo, V.C., Daniel, C., Yun, C., Marco, C., Yari, C., Hans, C.C., Emiliano, D., Carrie, A.D., Michael, D., Alexander, D.D., Taeko, D., Finn, D., Albert S, B.E., Matthias, E., Karl, E., Mitsuhiro, E., Hideki, E., Michela, F., Lynsey, F., Hai, F., Mary, C.F., Geoffrey, J.F., Alexander, V.F., Malcolm, E.F., Martin, C.F., Rie, F., Shiro, F., Cesare, F., Masaaki, F., Jun-ichi, F., Teunis, B.G., Andrew, G., Thomas, G., Daniel, G., Julian, G., Sven, G., Reto, G., Stefano, G., Thomas, J.H., Masahide, H., Mitsuko, H., Matthias, H., Jayson, H., Akira, H., Yuki, H., Takehiro, H., Meenhard, H., Kelly, J.H., Shannan, J.H.S., Oliver, M.H., Ilka, H., Fumi, H., Lukasz, H., Kei, I., Tomokatsu, I., Boris, R.J., Hui, J., Anagha, J., Giuseppe, J., Bogumil, K., Chieko, K., Kaoru, K., Kaiho, A., Kazuhiro, K., Mutsumi, K., Artem, S.K., Takeya, K., Shintaro, K., Sachi, K., Shuji, K., Hiroshi, K., Yuki, I.K., Tsugumi, K., Judith, S.K., Tony, J.K., Juha, K., Levon, M.K., Toshio, K., S Peter Klinken, Alan, J.K., Miki, K., Soichi, K., Naoto, K., Haruhiko, K., Shigeo, K., Sarah, K., Atsutaka, K., Andrew, T.K., Jeroen F, J.L., Weonju, L., Andreas, L., Kang, L., Berit, L., Leonard, L., Alan, M., Ri-ichiroh, M., Jessica, C.M., Benoit, M., Anthony, M., Niklas, M., Alison, M., Yosuke, M., David, A.D.L.M., Hiromasa, M., Mitsuru, M., Kazuyo, M., Efthymios, M., Hozumi, M., Christine, L.M., Mitsuyoshi, M., Sayaka, N., Yutaka, N., Fumio, N., Toshiyuki, N., Yukio, N., Kenichi, N., Erik van Nimwegen, Noriko, N., Hiromi, N., Shohei, N., Tadasuke, N., Soichi, O., Naganari, O., Hiroko, O., Hiroshi, O., Mitsuhiro, O., Mariko, O., Yasushi, O., Valerio, O., Dmitry, A.O., Arnab, P., Robert, P., Margaret, P., Helena, P., Silvano, P., James G, D.P., Owen J, L.R., Jordan, A.R., Mamoon, R., Timothy, R., Patrizia, R., Marco, R., Sugata, R., Morten, B.R., Eri, S., Antti, S., Akiko, S., Shimon, S., Mizuho, S., Hiroki, S., Hironori, S., Suzana, S., Alka, S., Claudio, S., Erik, A.S., Gundula, G.S., Anita, S., Thierry, S., Guojun, S., Hisashi, S., Yishai, S., Jay, W.S., Christophe, S., Daisuke, S., Takaaki, S., Masanori, S., Naoko, S., Rolf, K.S., Peter A, C.'.H., Michihira, T., Naoko, T., Jun, T., Hiroshi, T., Hideki, T., Zuotian, T., Mark, T., Hiroo, T., Tetsuro, T., Eivind, V., Marc van de Wetering, Linda, M.V.D.B., Roberto, V., Dipti, V., Ilya, E.V., Wyeth, W.W., Shoko, W., Christine, A.W., Louise, N.W., Ernst, W., Emily, J.W., Yoko, Y., Masayuki, Y., Misako, Y., Yohei, Y., Shigehiro, Y., Suzan, E.Z., Peter, G.Z., Xiaobei, Z., Silvia, Z., Kim, M.S., Harukazu, S., Carsten, O.D., Jun, K., Peter, H., Winston, H., Tom, C.F., Boris, L., Vladimir, B.B., Martin, S.T., Vsevolod, J.M., Albin, S., David, A.H., Piero, C., Yoshihide HayashizakSuzuki, H., Hjelt Institute (-2014), Forensic Medicine, PaleOmics Laboratory, Amsterdam institute for Infection and Immunity, Infectious diseases, Experimental Immunology, and Hubrecht Institute for Developmental Biology and Stem Cell Research
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Stage-Specific Embryonic Antigens ,Chromosomal Proteins, Non-Histone ,Cellular differentiation ,Basic fibroblast growth factor ,Gene Expression ,LINES ,OXYGEN ,chemistry.chemical_compound ,0302 clinical medicine ,Piperidines ,Phosphorylation ,STAT3 ,Induced pluripotent stem cell ,Cells, Cultured ,Chemokine CCL2 ,0303 health sciences ,Multidisciplinary ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,PROLIFERATION ,Cell Differentiation ,319 Forensic science and other medical sciences ,Nanog Homeobox Protein ,Immunohistochemistry ,Cell Hypoxia ,Cell biology ,HUMAN EMBRYONIC STEM ,GROUND-STATE ,Fibroblast Growth Factor 2 ,INACTIVATION ,Signal transduction ,Stem cell ,Signal Transduction ,Pluripotent Stem Cells ,STAT3 Transcription Factor ,EXPRESSION ,Immunoblotting ,Induced Pluripotent Stem Cells ,Kruppel-Like Transcription Factors ,Settore BIO/11 - Biologia Molecolare ,Alkenes ,Article ,Kruppel-Like Factor 4 ,03 medical and health sciences ,Humans ,Janus Kinases ,030304 developmental biology ,Homeodomain Proteins ,Proteins ,Janus Kinase 1 ,CAP ANALYSIS ,SELF-RENEWAL ,chemistry ,Epiblast ,INDUCIBLE FACTOR-I ,Immunology ,biology.protein ,030217 neurology & neurosurgery - 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 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.
- Published
- 2014
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