The phenotypes of pluripotent human hepatic progenitors.
Human livers contain two pluripotent hepatic progenitors, hepatic stem cells and hepatoblasts, with size, morphology, and gene expression profiles distinct from that of mature hepatocytes. Hepatic stem cells, the precursors to hepatoblasts, persist in stable numbers throughout life, and those isolated from the livers of all age donors from fetal to adult are essentially identical in their gene and protein expression profiles. The gene expression profile of hepatic stem cells throughout life consists of high levels of expression of cytokeratin 19 (CK19), neuronal cell adhesion molecule (NCAM), epithelial cell adhesion molecule (EpCAM), and claudin-3 (CLDN-3); low levels of albumin; and a complete absence of expression of alpha-fetoprotein (AFP) and adult liver-specific proteins. By contrast, hepatoblasts, the dominant cell population in fetal and neonatal livers, decline in numbers with age and are found as <0.1% of normal adult livers. They express high levels of AFP, elevated levels of albumin, low levels of expression of adult liver-specific proteins, low levels of CK19, and a loss of NCAM and CLDN-3. Mature hepatocytes lack expression altogether of EpCAM, NCAM, AFP, CLDN-3, cytokeratin 19, and have acquired the well-known adult-specific profile that includes expression of high levels of albumin, cytochrome P4503A4, connexins, phosphoenolpyruvate carboxykinase, and transferrin. Thus, hepatic stem cells have a unique stem cell phenotype, whereas hepatoblasts have low levels of expression of both stem cell genes and genes expressed in high levels in mature hepatocytes.
Schmelzer
Eva
E
Department of Cell and Molecular Biology, University of North Carolina School of Medicine, Campus Box 7038, Glaxo Building Rooms 32-35, Chapel Hill, 27599, USA. stemcell@med.unc.edu
Wauthier
Eliane
E
Reid
Lola M
LM
D000328:Adult; D000951:Antigens, Neoplasm / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D002648:Child; D062465:Claudin-3; D017630:Connexins / Q000235:genetics; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D000071858:Epithelial Cell Adhesion Molecule; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D053539:Keratin-19 / Q000235:genetics; D008099:Liver / Q000166:cytology* / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012709:Serum Albumin / Q000235:genetics; D000075462:Serum Albumin, Human; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014168:Transferrin / Q000235:genetics; D000509:alpha-Fetoproteins / Q000235:genetics
C422455:ALB protein, human; D000951:Antigens, Neoplasm; C568122:CLDN3 protein, human; D015815:Cell Adhesion Molecules; D062465:Claudin-3; D017630:Connexins; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D006023:Glycoproteins; D053539:Keratin-19; D008565:Membrane Proteins; D012709:Serum Albumin; D014168:Transferrin; D000509:alpha-Fetoproteins; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D000075462:Serum Albumin, Human