StemMACS™ CHIR99021 is a selective small molecule GSK3 inhibitor that activates Wnt signaling.
Background information
StemMACS™ CHIR99021 is a highly selective inhibitor of glycogen synthase kinase 3 (GSK-3), a crucial regulator of the Wnt signaling pathway. The aminopyridine CHIR99021 inhibits both GSK-3 isoforms, GSK-3α (IC50 10 nM) and GSK-3β (IC50 6.7 nM). Unlike other GSK-3 inhibitors, it does not cross-react with cyclin-dependent kinases (CDKs). Activation of Wnt signaling via CHIR99021-mediated GSK-3 inhibition is widely used to modulate pluripotent stem cell differentiation and self-renewal.
Applications
Published applications for CHIR99021 include:
Naïve, ground state culture of murine ES and iPS cells using 2i conditions1
Naïve, ground state culture of rat ES and iPS cells using 3i conditions2
Naïve, ground state culture of human ES and iPS cells3
Differentiation of human ES and iPS cells into cardiomyocytes4
Differentiation of human ES and iPS cells into skeletal muscle5
Differentiation of human ES and iPS cells into definitive endoderm6
Solbrant, S. et al. (2017) Generation of high-purity human ventral midbrain dopaminergic progenitors for in vitro maturation and intracerebral transplantation Nat. Protoc. 12(9): 1962-1979
Ying, Q. L. et al. (2008) The ground state of embryonic stem cell self-renewal. Nature 453: 519-523
Li et al. (2008) Germline competent embryonic stem cells derived from rat blastocysts. Cell 135: 1299-1310
Gafni, O. et al. (2013) Derivation of novel human ground state naive pluripotent stem cells. Nature 504: 282-286
Lian, X. et al. (2012) Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc. Natl. Acad. Sci. U.S.A. 109(27): E1848-1857
Borchin, B. et al. (2013) Derivation and FACS-mediated purification of PAX3+/PAX7+ skeletal muscle precursors from human pluripotent stem cells. Stem Cell Reports 1: 620-631
Teo, A. K. K. et al. (2014) Comparable generation of activin-induced definitive endoderm via additive Wnt or BMP signaling in absence of serum. Stem Cell Reports 3: 5-14
Hou, P. et al. (2013) Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science 341(6146): 651-654