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Generation of Liver Bipotential Organoids With a Small-Molecule Cocktail
Understanding the mechanism of how cholangiocytes (liver ductal cells) are activated upon liver injury and specified to hepatocytes would permit liver regenerative medicine. Here we achieved long-term in vitro expansion of mouse liver organoids by modulating signaling pathways with a combination of three small-molecule compounds. CHIR-99021, Blebbistatin, and Forskolin together maintained the liver organoids in bipotential stage with both cholangiocyte and hepatocyte-specific gene expression profiles and enhanced capacity for further hepatocyte differentiation. By employing a chemical approach, we demonstrated that Wnt/β-catenin, NMII-Rac, and PKA-ERK are core signaling pathways essential and sufficient for mouse liver progenitor expansion. Moreover, the advanced small-molecule culture of bipotential organoids facilitates the ex vivo investigation of liver cell fate determination and the application of organoids in liver regenerative medicine.
Related Products
| Cat.No. | Product Name | Information |
|---|---|---|
| S2924 | Laduviglusib (CHIR-99021) HCl | Laduviglusib (CHIR-99021; CT99021) HCl is hydrochloride of CHIR-99021, which is a GSK-3α/β inhibitor with IC50 of 10 nM/6.7 nM; CHIR-99021 shows greater than 500-fold selectivity for GSK-3 versus its closest homologs Cdc2 and ERK2. CHIR-99021 is a potent pharmacological activators of the Wnt/beta-catenin signaling pathway. CHIR-99021 significantly rescues light-induced autophagy and augments GR, RORα and autophagy-related proteins. |
Related Targets
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