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Tissue-Specific Stem Cells |
1 Department of Cell and Molecular Physiology, UNC School of Medicine, Chapel Hill, North Carolina
* To whom correspondence should be addressed. E-mail: stemcell{at}med.unc.edu.
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Abstract |
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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 consist of high levels of expression of cytokeratin 19 (CK19), neuronal cell adhesion molecule (N-CAM), epithelial cell adhesion molecule (EpCAM), claudin-3 (CLDN-3), low levels of albumin, and a complete absence of expression of alpha-fetoprotein (AFP) and adult liverspecific 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.
Key Words. liver, stem cell, hepatoblast, progenitor, EpCAM, NCAM, hepatocyte, gene expression, alpha-fetoprotein
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