Table 1.

Niche factors and supplement for lung normal organoids.

Niche Factor	Supplement	Role	Functions	Ref.
WNT	WNT3a	WNT ligand	initiates the canonical Wnt/β-catenin pathway. WNT3a is required to the clonal expansion of Alveolar type 2 cells Airway organoid is not required the addition of exogenous WNT3a.	[45,117,118]
	CHIR99021	GSK3 Inhibitor	stimulate the WNT/β-catenin signaling strong wnt signaling impairs the formation of airwary organoid	[119,120]
	R-spondin	agonist	amplifies the WNT/β-catenin signaling. require the expansion and long-term culture of airway organoid.	[45,117,118]
BMP	Noggin	BMP inhibitor	increases the number of stem cells and blocks their differentiation. maintains the stemness of stem cells.	[112,117,119]
TGF-b	SB431542	ALK5 inhibitor	lengthen organoid growth	[119,120]
	A83-01	ALK4/5/7 inhibitor	prevents TGF-β induced growth inhibition.	[121]
FGF	FGF2	FGFR ligand	keeps the survival of organoids. produce large organoids and induce organoid branching	[118]
	FGF7	FGFR ligand	promotes differentiation of lung stem cells toward distal lung lineages. induces organoid branching.	[118,119,120]
	FGF10	FGFR ligand	promotes differentiation of lung stem cells toward distal lung lineages. induces organoid branching.	[118,120]
EGF	EGF	EGFR ligand	drive proliferation of organoids. not essential for organoid formation, but it increases the size of alveolar organoids	[117]
p38 MAPK	SB202190	p38 MAPK inhibitor	to overcome organoid growth arrest protects cells from environmental stress induced apoptosis.	[45]