Open AccessSelf‐Renewal Versus Lineage Commitment of Embryonic Stem Cells: Protein Kinase C Signaling Shifts the Balance
Author(s) -
Dutta Debasree,
Ray Soma,
Home Pratik,
Larson Melissa,
Wolfe Michael W.,
Paul Soumen
Publication year - 2011
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.605
Subject(s) - biology , embryonic stem cell , microbiology and biotechnology , stem cell , lineage (genetic) , signal transduction , kinase , genetics , gene
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. S TEM C ells 2011;29:618–628