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 language | English (US) |
|---|---|
| Pages (from-to) | 139-152 |
| Number of pages | 14 |
| Journal | Stem Cell Research |
| Volume | 12 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2014 |
Bibliographical note
Funding Information:We thank Hitoshi Niwa (Laboratory for Pluripotent Cell Studies) and Benjamin Madden (Mayo Clinic for LTQ analysis). This work was supported by The Hormel Foundation , the Mayo Foundation , and the University of Minnesota .
