Document Detail


Fate tracing of mature hepatocytes in mouse liver homeostasis and regeneration.
MedLine Citation:
PMID:  22105172     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent evidence has contradicted the prevailing view that homeostasis and regeneration of the adult liver are mediated by self duplication of lineage-restricted hepatocytes and biliary epithelial cells. These new data suggest that liver progenitor cells do not function solely as a backup system in chronic liver injury; rather, they also produce hepatocytes after acute injury and are in fact the main source of new hepatocytes during normal hepatocyte turnover. In addition, other evidence suggests that hepatocytes are capable of lineage conversion, acting as precursors of biliary epithelial cells during biliary injury. To test these concepts, we generated a hepatocyte fate-tracing model based on timed and specific Cre recombinase expression and marker gene activation in all hepatocytes of adult Rosa26 reporter mice with an adenoassociated viral vector. We found that newly formed hepatocytes derived from preexisting hepatocytes in the normal liver and that liver progenitor cells contributed minimally to acute hepatocyte regeneration. Further, we found no evidence that biliary injury induced conversion of hepatocytes into biliary epithelial cells. These results therefore restore the previously prevailing paradigms of liver homeostasis and regeneration. In addition, our new vector system will be a valuable tool for timed, efficient, and specific loop out of floxed sequences in hepatocytes.
Authors:
Yann Malato; Syed Naqvi; Nina Schürmann; Raymond Ng; Bruce Wang; Joan Zape; Mark A Kay; Dirk Grimm; Holger Willenbring
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-11-21
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  121     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-02     Completed Date:  2012-01-31     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4850-60     Citation Subset:  AIM; IM    
Affiliation:
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, UCSF, San Francisco, California, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bacterial Proteins / analysis,  genetics
Carbon Tetrachloride Poisoning / pathology
Cell Lineage
Dependovirus / genetics
Drug-Induced Liver Injury / pathology
Epithelial Cells / pathology
Genes, Reporter
Genetic Vectors / genetics
Hepatectomy
Hepatic Duct, Common / injuries,  pathology
Hepatocytes / cytology*
Homeostasis / physiology*
Integrases / genetics
Liver / injuries,  pathology,  physiology*
Liver Regeneration / physiology*
Luminescent Proteins / analysis,  genetics
Mice
Mice, Inbred C57BL
Prealbumin / genetics
Pyridines / toxicity
Species Specificity
Stem Cells / cytology
Transgenes
Grant Support
ID/Acronym/Agency:
P30 DK026743/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/3,5-diethoxycarbonyl-1,4-dihydrocollidine; 0/Bacterial Proteins; 0/Luminescent Proteins; 0/Prealbumin; 0/Pyridines; 0/yellow fluorescent protein, Bacteria; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases
Comments/Corrections
Comment In:
Hepatology. 2012 Jun;55(6):2024-7   [PMID:  22407729 ]
J Clin Invest. 2011 Dec;121(12):4630-3   [PMID:  22105167 ]

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