. 2021 Aug 22;74(2):1101–1116. doi: 10.1002/hep.31705

TABLE 2.

A Nonexhaustive Overview of the Principal Steps in the Liver Embryonic Development and Their Equivalents During the Hepatocyte Differentiation of PSCs

Steps	In Vivo	In Vitro
Steps	Embryonic Development	Growth Factors	Markers
Definitive endoderm	Activin/Notch pathway	Activin A (TGFβ family)	CXCR4, SOX17, HNF3β, GATA4
Endoderm specification	Factor secretion by the septum transversum	Bone morphogenetic protein 4/2	Alpha‐fetoprotein, hepatocyte nuclear factor 4α
Endoderm specification	Factor secretion by the developing heart	FGF2/4	Alpha‐fetoprotein, hepatocyte nuclear factor 4α
Hepatoblast differentiation into hepatocytes and maturation	Members of the hepatocyte nuclear factor family	Hepatocyte growth factor	Hepatocyte nuclear factor 4α, alpha‐1‐anti‐trypsin, CYP3A7
	Inhibition of Notch and TGFβ pathways	Oncostatin M	Hepatocyte functions: albumin or urea secretion, energy metabolism, detoxification
	Inhibition of Notch and TGFβ pathways	Dexamethasone

Additional data are available in Supporting Table S2.

Abbreviations: CXCR4, chemokine (C‐X‐C motif) receptor 4; GATA4, GATA binding protein 4; HNF, hepatocyte nuclear factor; SOX17, SRY (sex determining region Y)‐box 17.