Stem Cell Research (Jan 2014)

JNK1 and 2 play a negative role in reprogramming to pluripotent stem cells by suppressing Klf4 activity

  • Ke Yao,
  • Myoung Ok Ki,
  • Hanyong Chen,
  • Yong-Yeon Cho,
  • Sung-Hyun Kim,
  • Dong Hoon Yu,
  • Sung-Young Lee,
  • Kun-Yeong Lee,
  • Kibeom Bae,
  • Cong Peng,
  • Do Young Lim,
  • Ann M. Bode,
  • Zigang Dong

DOI
https://doi.org/10.1016/j.scr.2013.10.005
Journal volume & issue
Vol. 12, no. 1
pp. 139 – 152

Abstract

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Embryonic stem (ES) cells are pluripotent cells with the capacity for unlimited self-renewal or differentiation. Inhibition of MAPK pathways enhances mouse ES cell pluripotency characteristics. Compared to wildtype ES cells, jnk2−/− ES cells displayed a much higher growth rate. To determine whether JNKs are required for stem cell self-renewal or differentiation, we performed a phosphorylation kinase array assay to compare mouse ES cells under LIF+ or LIF− culture conditions. The data showed that activation of JNKs was induced by LIF withdrawal. We also found that JNK1 or 2 phosphorylated Klf4 at threonines 224 and 225. Activation of JNK signaling and phosphorylation of Klf4 inhibited Klf4 transcription and transactivation activity. Importantly, jnk1−/− and jnk2−/− murine embryonic fibroblasts (MEFs) exhibited a significantly greater potency in the ability to increase the number of iPS colonies compared with jnk wildtype MEFs. Overall, our results demonstrated that JNK1 and 2 play a negative role in reprogramming to pluripotent stem cells by suppressing Klf4 activity.