The hepatic stem cell niche: identification by label-retaining cell assay.
Label retention assays remain the state-of-the-art approach to identify the location of intraorgan epithelial stem cell niches, in situ and in vivo. They are commonly used in organs with rapid cell turnover but have not been applied to the liver, where cell turnover is very slow. We used a sublethal dose of acetaminophen administered coincident with bromodeoxyuridine to load possible hepatic stem cells in mice with label and then administered a second, sublethal chase of acetaminophen to accomplish "washout" of label from transit amplifying cell populations.


CONCLUSIONS
Four possible hepatic stem cell niches are identified by this approach: the canal of Hering (proximal biliary tree), intralobular bile ducts, periductal "null" mononuclear cells, and peribiliary hepatocytes. These results confirm several different and often contradictory lines of investigation regarding the intrahepatic location of stem/progenitor cells and suggest that the liver has a multi-tiered, flexible system of regeneration rather than a single stem/progenitor cell location.
Kuwahara
Reiichiro
R
Department of Medicine, Division of Digestive Diseases, Beth Israel Medical Center-Albert Einstein College of Medicine, New York, NY 10003, USA.
Kofman
Alexander V
AV
Landis
Charles S
CS
Swenson
E Scott
ES
Barendswaard
Els
E
Theise
Neil D
ND
D000082:Acetaminophen / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D001652:Bile Ducts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D001973:Bromodeoxyuridine