Hepatic stem cells and their mesenchymal partners, angioblasts, give rise to daughter cells maturing into lineages
of parenchymal and mesenchymal cells with stepwise changes in cell size, morphology, ploidy, gene expression, growth potential, and signaling.1-4 Currently, there is selleck chemicals llc evidence for at least eight intrahepatic lineage stages (Figs. 1, 2).5, 6 Continued efforts to characterize the liver’s lineage biology should result in recognition of additional stages. This overview focuses on early intrahepatic lineage stages in human livers and includes aspects of their regulation. Information on later lineage stages of cells, and additional background and references are included in the online supplement. Hepatic stem cells (hHpSCs) are multipotent stem cells located within the liver’s stem cell compartment, the ductal plates of fetal and neonatal livers, and canals of Hering in pediatric and adult livers.5, 7-12 The compartment represents the anatomic and physiological link between the intralobular
canalicular system of hepatocytes and the biliary tree and resides along sites that project starlike from the portal tracts. They constitute ≈0.5%-2% of the Mannose-binding protein-associated serine protease parenchyma of livers of all age donors. The hHpSCs cells range in size from 7-9 μm in diameter and have a high nucleus-to-cytoplasm Selleckchem Atezolizumab ratio. Tolerant of ischemia, they can remain viable in cadaveric livers for up to ≈6 days after asystolic death.11, 12 The hHpSC phenotypic profile includes epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule (NCAM), CD133, CXCR4, SOX9, SOX17, FOXA2,
cytokeratins (CK) 8/18/19, Hedgehog proteins (Sonic and Indian), intranuclear telomerase protein, claudin 3, MDR1, weak or negligible expression of albumin and major histocompatibility complex (MHC) antigens. They do not express α-fetoprotein (AFP), intercellular adhesion molecule (ICAM-1), P450s, or markers for hemopoietic (e.g., CD34/38/45/90, glycophorin), endothelial (e.g., vascular endothelial growth factor receptor [VEGFr], CD31, von Willebrand factor), or mesenchymal cells (e.g., CD146, desmin, vitamin A, CD105).6, 7, 13 It remains unclear whether C-kit (CD117), expressed in the liver’s stem cell niches,8, 14, 15 is on hHpSCs or associated angioblasts, as CD117+ flow cytometry selects for angioblasts.