CHIR 99021 is a potent and highly selective inhibitor of glycogen synthase kinase 3 (GSK-3), with IC50 values of 6.7 and 10 nM for GSK-3 beta and GSK-3 alpha respectively, and greater than >500-fold selectivity for GSK-3 over closely related kinases. CHIR 99021 in combination with other agents can be used to reprogram mouse embryonic fibroblasts into induced pluripotent stem cells (iPSCs) and can also enhance mouse and human embryonic stem cell (ESC) self-renewal and promote differentiation of human pluripotent stem cells (hPSCs) in cardiomyocytes. CHIR 99021 is used in a protocol to generate brain organoids from human iPSCs.