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SB216763 is a cell-permeable ATP-competitive inhibitor of glycogen synthase kinase 3α (GSK3α, IC₅₀ = 34 nM) and GSK3β isozymes (Coghlan et al.). GSK3 is a serine/threonine protein kinase that is inhibited by a variety of extracellular stimuli including insulin, growth factors, cell specification factors, and cell adhesion.
MAINTENANCE AND SELF-RENEWAL
· Maintains mouse embryonic stem (ES) cells in an undifferentiated, pluripotent state for up to two months when co-cultured with mouse embryonic fibroblasts (MEFs) in the absence of leukemia inhibitory factor (LIF; Kirby et al.).
· Promotes the proliferation of primary mouse retinal stem cells (Inoue et al.).
· Increases neural progenitor proliferation in mouse brains (Mao et al.).
· Increases symmetric division of neural stem cells (NSCs) in in vivo and in vitro models of the adult mouse brain (Piccin and Morshead).
· Inhibits adipocyte differentiation in human mesenchymal stem cells (MSCs; Shen et al.).
· Promotes the generation of hematopoietic stem cells (HSCs) in aorta-gonad-mesonephros (AGM) explant cultures (Ruiz-Herguido et al.).
DIFFERENTIATION
· Enhances the insulin-induced differentiation of quiescent reserve cells from cultured mouse myoblasts (Rochat et al.).
· Stimulates NSC differentiation in cultured rat neurospheres (Maurer et al.).
· Induces neuronal differentiation in cultured human neural progenitor cells (NPCs; Lange et al.).
· Promotes differentiation of dendritic cells from cultured mouse hematopoietic progenitor cells (HPCs; Zhou et al.).
CANCER RESEARCH
· Induces differentiation and reduces the cancer stem cell population of cultured human glioblastoma cells (Korur et al.).
Cell Type
Cancer Cells and Cell Lines, Dendritic Cells, Hematopoietic Stem and Progenitor Cells, Mesenchymal Stem and Progenitor Cells, Myogenic Stem and Progenitor Cells, Neural Stem and Progenitor Cells, Pluripotent Stem Cells
This product is designed for use in the following research area(s) as part
of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we
offer to support each research area.
Hematopoietic stem cell development requires transient Wnt/β-catenin activity.
Ruiz-Herguido C et al.
The Journal of experimental medicine 2012 JUL
Abstract
Understanding how hematopoietic stem cells (HSCs) are generated and the signals that control this process is a crucial issue for regenerative medicine applications that require in vitro production of HSC. HSCs emerge during embryonic life from an endothelial-like cell population that resides in the aorta-gonad-mesonephros (AGM) region. We show here that β-catenin is nuclear and active in few endothelial nonhematopoietic cells closely associated with the emerging hematopoietic clusters of the embryonic aorta during mouse development. Importantly, Wnt/β-catenin activity is transiently required in the AGM to generate long-term HSCs and to produce hematopoietic cells in vitro from AGM endothelial precursors. Genetic deletion of β-catenin from the embryonic endothelium stage (using VE-cadherin-Cre recombinase), but not from embryonic hematopoietic cells (using Vav1-Cre), precludes progression of mutant cells toward the hematopoietic lineage; however, these mutant cells still contribute to the adult endothelium. Together, those findings indicate that Wnt/β-catenin activity is needed for the emergence but not the maintenance of HSCs in mouse embryos.
Glycogen synthase kinase 3 (GSK3) inhibitor, SB-216763, promotes pluripotency in mouse embryonic stem cells.
Kirby LA et al.
PloS one 2012 JAN
Abstract
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.
Wnt signaling regulates symmetry of division of neural stem cells in the adult brain and in response to injury.
Piccin D and Morshead CM
Stem cells (Dayton, Ohio) 2011 MAR
Abstract
Neural stem cells comprise a small population of subependymal cells in the adult brain that divide asymmetrically under baseline conditions to maintain the stem cell pool and divide symmetrically in response to injury to increase their numbers. Using in vivo and in vitro models, we demonstrate that Wnt signaling plays a role in regulating the symmetric divisions of adult neural stem cells with no change in the proliferation kinetics of the progenitor population. Using BAT-gal transgenic reporter mice to identify cells with active Wnt signaling, we demonstrate that Wnt signaling is absent in stem cells in conditions where they are dividing asymmetrically and that it is upregulated when stem cells are dividing symmetrically, such as (a) during subependymal regeneration in vivo, (b) in response to stroke, and (c) during colony formation in vitro. Moreover, we demonstrate that blocking Wnt signaling in conditions where neural stem cells are dividing symmetrically inhibits neural stem cell expansion both in vivo and in vitro. Together, these findings reveal that the mechanism by which Wnt signaling modulates the size of the stem cell pool is by regulating the symmetry of stem cell division.
PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED. FOR ADDITIONAL INFORMATION ON QUALITY AT STEMCELL, REFER TO WWW.STEMCELL.COM/COMPLIANCE.