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. 2018 Feb 12;8:2821. doi: 10.1038/s41598-018-21121-6

Figure 2.

Figure 2

Induction of differentiation of IHCC organoids to functional hepatocytes. (a) Schedule for hepatocyte differentiation using IHCC organoids. IHCC organoids were cultured for 7–10 days in EM additionally supplemented with BMP7. Then, the culture medium was changed to DM. DM was changed every 2–3 days for a period of 12 days. GSEA was performed using a ‘hepatocyte differentiation’ gene set. IHCC organoids cultured in DM have a strongly enriched hepatocyte differentiation signature (p < 0.01, FDR < 0.01). (b) Relative expression of Albumin (ALB), CYP3A4 and HNF4A in IHCC organoids cultured in EM or DM. (c) Albumin secretion, CYP3A4 activity and bile acid production in IHCC organoids cultured in EM or DM. (d) Relative expression of Albumin (ALB), CYP3A4 and HNF4A in IHCC organoids cultured in EM, or in EM without R-spondin 1 (Rspo).