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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 5 APR 2011
Copyright © 2011 AlphaMed Press
Volume 29, Issue 4, pages 618–628, April 2011
How to Cite
Dutta, D., Ray, S., Home, P., Larson, M., Wolfe, M. W. and Paul, S. (2011), Self-Renewal Versus Lineage Commitment of Embryonic Stem Cells: Protein Kinase C Signaling Shifts the Balance. STEM CELLS, 29: 618–628. doi: 10.1002/stem.605
Disclosure of potential conflicts of interest is found at the end of this article.
Author contributions: D.D., S.R., P.H., and M.L.: performed experiments; M.W.W.: provided reagents and designed experiments; S.P.: designed experiments and wrote the manuscript.
First published online in STEM CELLSEXPRESS February 3, 2011.
- Issue published online: 5 APR 2011
- Article first published online: 5 APR 2011
- Accepted manuscript online: 3 FEB 2011 01:14PM EST
- Manuscript Accepted: 8 JAN 2011
- Manuscript Received: 4 OCT 2010
- NIH. Grant Numbers: HL094892, P20 RRO24214, HD062546
- Protein Kinase C;
- Embryonic Stem cells;
- Induced pluripotency
The intricate molecular mechanisms that regulate ESC pluripotency are incompletely understood. Prior research indicated that activation of the Janus kinase–signal transducer and activator of transcription (STAT3) pathway or inhibition of extracellular signal-regulated kinase/glycogen synthase kinase 3 (ERK/GSK3) signaling maintains mouse ESC (mESC) pluripotency. Here, we demonstrate that inhibition of protein kinase C (PKC) isoforms maintains mESC pluripotency without the activation of STAT3 or inhibition of ERK/GSK3 signaling pathways. Our analyses revealed that the atypical PKC isoform, PKCζ plays an important role in inducing lineage commitment in mESCs through a PKCζ–nuclear factor kappa-light-chain-enhancer of activated B cells signaling axis. Furthermore, inhibition of PKC isoforms permits derivation of germline-competent ESCs from mouse blastocysts and also facilitates reprogramming of mouse embryonic fibroblasts toward induced pluripotent stem cells. Our results indicate that PKC signaling is critical to balancing ESC self-renewal and lineage commitment. STEM Cells 2011;29:618–628