Glycogen synthase kinase 3 (GSK3) inhibitor, SB-216763, promotes pluripotency in mouse embryonic stem cells

Canonical Wnt/β-catenin signaling has been suggested to promote self-renewal of pluripotent mouse and human embryonic stem cells. Here, we show that SB-216763, a glycogen synthase kinase-3 (GSK3) inhibitor, can maintain mouse embryonic stem cells (mESCs) in a pluripotent state in the absence of exog...

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Bibliographic Details
Published in:PloS one 2012-06, Vol.7 (6), p.e39329-e39329
Main Authors: Kirby, Leslie A, Schott, Jason T, Noble, Brenda L, Mendez, Daniel C, Caseley, Paul S, Peterson, Sarah C, Routledge, Tyler J, Patel, Nilay V
Format: Article
Language:English
Subjects:
Animals
beta Catenin - metabolism
Biology
Cell culture
Cell Differentiation - drug effects
Cell Line
Cell self-renewal
Colonies
Comparative analysis
Embryo cells
Embryo fibroblasts
Embryonic stem cells
Embryonic Stem Cells - cytology
Embryonic Stem Cells - drug effects
Enzyme inhibitors
Fibroblasts
Gene expression
Glycogen
Glycogen synthase kinase 3
Glycogen Synthase Kinase 3 - antagonists & inhibitors
Glycogen synthesis
Heart diseases
Humans
Immunohistochemistry
Indoles - pharmacology
Inhibitors
Kinases
Leukemia
Leukemia inhibitory factor
Maleimides - pharmacology
Metabolism
Mice
Neurons - cytology
Neurons - drug effects
Oct-4 protein
Phosphorylation
Pluripotency
Polymerase Chain Reaction
Science
Signal transduction
Signaling
Stem cell transplantation
Stem cells
Transcription factors
Trends
Tumorigenesis
Wnt protein
β-Catenin
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Summary:Canonical Wnt/β-catenin signaling has been suggested to promote self-renewal of pluripotent mouse and human embryonic stem cells. Here, we show that SB-216763, a glycogen synthase kinase-3 (GSK3) inhibitor, can maintain mouse embryonic stem cells (mESCs) in a pluripotent state in the absence of exogenous leukemia inhibitory factor (LIF) when cultured on mouse embryonic fibroblasts (MEFs). MESCs maintained with SB-216763 for one month were morphologically indistinguishable from LIF-treated mESCs and expressed pluripotent-specific genes Oct4, Sox2, and Nanog. Furthermore, Nanog immunostaining was more homogenous in SB-216763-treated colonies compared to LIF. Embryoid bodies (EBs) prepared from these mESCs expressed early-stage markers for all three germ layers, and could efficiently differentiate into cardiac-like cells and MAP2-immunoreactive neurons. To our knowledge, SB-216763 is the first GSK3 inhibitor that can promote self-renewal of mESC co-cultured with MEFs for more than two months.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0039329