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

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)139-152
Number of pages14
JournalStem Cell Research
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2014

Fingerprint Dive into the research topics of 'JNK1 and 2 play a negative role in reprogramming to pluripotent stem cells by suppressing Klf4 activity'. Together they form a unique fingerprint.

  • Cite this

    Yao, K., Ki, M. O., Chen, H., Cho, Y. Y., Kim, S. H., Yu, D. H., Lee, S. Y., Lee, K. Y., Bae, K., Peng, C., Lim, D. Y., Bode, A. M., & Dong, Z. (2014). JNK1 and 2 play a negative role in reprogramming to pluripotent stem cells by suppressing Klf4 activity. Stem Cell Research, 12(1), 139-152. https://doi.org/10.1016/j.scr.2013.10.005