Table 1.

List of PF and HSC Features in Quiescence and Activation

Localization in liver	PFs	HSCs
	Portal vein	Space of Disse
Morphology
Quiescent state	•Flat •Spindle-shaped cells •Dark, oval nucleus •Actively secrete ECM	•Stellate-like shape •Reduced cellular body volume •Spindle-shaped • Voluminous oval or elongated nucleus ○ Often compressed by vitamin A and/or retinoid containing lipid drops placed in the perinuclear cytoplasm •Dilated, rough endoplasmic reticulum •Low number of mitochondria and lysosomes
Activated state	•Spindle-shaped cells • Smooth muscle-like features: ○ Contractile apparatus ○ Prominent rough endoplasmic reticulum ○ Golgi apparatus producing collagen ○ Peripheral myofilaments ○ Fibronexus (no lamina) ○ Gap junctions	•Loss of retinoid/vitamin A lipid droplets •Flat-stellate shape •Expression of contractile fibers (myofibroblast differentiation – contractility) in cytoplasm •Matured rough endoplasmic reticulum associated with a well-formed Golgi apparatus
Functions
Quiescent state	•Maintain integrity of the biliary tree and portal tract	•Balanced ECM turnover •Low proliferation •Storage of vitamin A and retinoids
Activated state	•Proliferative •Contribute to collagen type I deposition •Regulate cholangiocyte proliferation •Maintain cholangiocyte polarity •Support angiogenesis	•Fibrogenesis •ECM synthesis and degradation •Increased cell proliferation •Contractility •Secretion of cytokines, chemokines, and immunomodulatory signals •Acts as antigen-presenting cells •Role in liver development and regeneration (hepatocyte proliferation) •Support angiogenesis and LSEC capillarization
Markers
Quiescent state	•Thy-1 •Fibulin-2 •Elastin •Gremlin-1 •ENTPD2 •IL-6	•Vitamin A •Retinoid •Desmin
Activated state	•Thy-1 •Mesothelin •Fibulin-2 •Elastin •Gremlin-1 •Asporin •IL-6 •Collagen 15A1 •Mucin 16 •ENTPD2 •Endoglin •CD73 •CD143 •ACTA2	•Glial fibrillary acidic protein •Neurotrophin receptor p75 •Synemin •Lecithin:retinol acyltransferase •ACTA2 •Reelin •Endoglin •CD73 •CD143
Injury response	•Primary responders of cholangiocyte damage	•Primary responders of hepatocyte damage
ECM synthesis	•Elastic fibers (elastin core surrounded by fibrillin-rich microfibrils) •Collagen XV	•Collagen I and III •Fibronectin •Thrombospondin-1 •Proteoglycans

ACTA2, alpha smooth muscle actin; CD, cluster of differentiation; ENTPD2, ectonucleotidase 2; LSEC, lymphatic sinusoidal endothelial cell; Thy-1, thymocyte differentiation antigen-1.