Self-renewal versus lineage commitment of embryonic stem cells: protein kinase C signaling shifts the balance.

Stem Cells

Department of Pathology and Laboratory Medicine, Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.

Published: April 2011

AI Article Synopsis

  • The mechanisms governing embryonic stem cell (ESC) pluripotency are not fully understood, with prior research linking the Janus kinase-STAT3 pathway and ERK/GSK3 signaling to mESC maintenance.
  • New findings show that inhibiting protein kinase C (PKC) isoforms can also preserve mESC pluripotency without activating STAT3 or inhibiting ERK/GSK3 pathways.
  • Specifically, the atypical PKC isoform, PKCζ, promotes lineage commitment in mESCs, indicating that PKC signaling is essential for balancing ESC self-renewal and differentiation.

Article 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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413330PMC
http://dx.doi.org/10.1002/stem.605DOI Listing

Publication Analysis

Top Keywords

lineage commitment
12
stem cells
8
protein kinase
8
erk/gsk3 signaling
8
mesc pluripotency
8
pkc isoforms
8
signaling
5
self-renewal versus
4
versus lineage
4
commitment embryonic
4

Similar Publications

Optimal embryonic development depends upon cell-signaling molecules released by the maternal reproductive tract called embryokines. Identity of specific embryokines that enhance competence of the embryo for sustained survival is largely lacking. The current objective was to evaluate effects of three putative embryokines in cattle on embryonic development to the blastocyst stage.

View Article and Find Full Text PDF

The cellular and molecular mechanisms underlying lymphocyte development are diverse among teleost species. Although recent scRNA-seq analyses of zebrafish hematopoietic cells have advanced our understanding of teleost hematopoiesis, comparative studies using another genetic model, medaka, which is evolutionarily distant among teleosts, is useful for understanding commonality and species-specificity in teleosts. In order to gain insight into how different molecular and cellular mechanisms of lymphocyte development in medaka and zebrafish, we established a () mutant medaka, which exhibited defects in V(D)J rearrangement of lymphocyte antigen receptor genes, accordingly lacking mature B and T cells.

View Article and Find Full Text PDF

Iron Drives Eosinophil Differentiation in Allergic Airway Inflammation Through Mitochondrial Metabolic Adaptation.

Adv Healthc Mater

January 2025

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China.

Eosinophils play a crucial role as effector cells in asthma pathogenesis, with their differentiation being tightly regulated by metabolic mechanisms. While the involvement of iron in various cellular processes is well known, its specific role in eosinophil differentiation has largely remained unexplored. This study demonstrates that iron levels are increased during the differentiation process from eosinophil progenitors to mature and activated eosinophils in the context of allergic airway inflammation.

View Article and Find Full Text PDF

Stomatal abundance sets plants' potential for gas exchange, impacting photosynthesis and transpiration and, thus, plant survival and growth. Stomata originate from cell lineages initiated by asymmetric divisions of protodermal cells, producing meristemoids that develop into guard cell pairs. The transcription factors SPEECHLESS, MUTE, and FAMA are essential for stomatal lineage development, sequentially driving cell division and differentiation events.

View Article and Find Full Text PDF

In vivo lineage tracing holds great potential to reveal fundamental principles of tissue development and homeostasis. However, current lineage tracing in humans relies on extremely rare somatic mutations, which has limited temporal resolution and lineage accuracy. Here, we developed a generic lineage-tracing tool based on frequent epimutations on DNA methylation, enabled by our computational method MethylTree.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!