Triple Staining Including FOXA2 Identifies Stem Cell Lineages Undergoing Hepatic and Biliary Differentiation in Cirrhotic Human Liver
| Autor: | Leslie E. Rogler, Remon Bebawee, Sanjeev Gupta, Joe S. Matarlo, Nicole Pattamanuch, Joseph Locker, Charles E. Rogler |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male Pathology medicine.medical_specialty Histology Cellular differentiation Biology 03 medical and health sciences Cytokeratin medicine Humans Cell Lineage Progenitor cell Aged Keratin-19 Staining and Labeling Liver cell Stem Cells Infant Cell Differentiation Articles Immunohistochemistry Endothelial stem cell 030104 developmental biology medicine.anatomical_structure Liver Hepatocyte Hepatocyte Nuclear Factor 3-beta Hepatocytes Female FOXA2 Bile Ducts Anatomy Stem cell |
| Popis: | Recent investigations have reported many markers associated with human liver stem/progenitor cells, “oval cells,” and identified “niches” in diseased livers where stem cells occur. However, there has remained a need to identify entire lineages of stem cells as they differentiate into bile ducts or hepatocytes. We have used combined immunohistochemical staining for a marker of hepatic commitment and specification (FOXA2 [Forkhead box A2]), hepatocyte maturation (Albumin and HepPar1), and features of bile ducts (CK19 [cytokeratin 19]) to identify lineages of stem cells differentiating toward the hepatocytic or bile ductular compartments of end-stage cirrhotic human liver. We identified large clusters of disorganized, FOXA2 expressing, oval cells in localized liver regions surrounded by fibrotic matrix, designated as “micro-niches.” Specific FOXA2-positive cells within the micro-niches organize into primitive duct structures that support both hepatocytic and bile ductular differentiation enabling identification of entire lineages of cells forming the two types of structures. We also detected expression of hsa-miR-122 in primitive ductular reactions expected for hepatocytic differentiation and hsa-miR-23b cluster expression that drives liver cell fate decisions in cells undergoing lineage commitment. Our data establish the foundation for a mechanistic hypothesis on how stem cell lineages progress in specialized micro-niches in cirrhotic end-stage liver disease. |
| Databáze: | OpenAIRE |
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