Self-Renewal Versus Lineage Commitment of Embryonic Stem Cells: Protein Kinase C Signaling Shifts the Balance§

Authors

  • Debasree Dutta,

    1. Department of Pathology and Laboratory Medicine, Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
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  • Soma Ray,

    1. Department of Pathology and Laboratory Medicine, Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
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  • Pratik Home,

    1. Department of Pathology and Laboratory Medicine, Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
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  • Melissa Larson,

    1. Transgenic and Gene Targeting Institutional Facility, University of Kansas Medical Center, Kansas City, Kansas, USA
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  • Michael W. Wolfe,

    1. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA
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  • Soumen Paul

    Corresponding author
    1. Department of Pathology and Laboratory Medicine, Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
    • Institute for Reproductive Health and Regenerative Medicine, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA
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    • Ph: 913-588-7236; Fax: 913-588-8287


  • 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.

Abstract

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

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