Locating the stem cell niche and tracing hepatocyte lineages in human liver
Open Access
- 23 December 2008
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 49 (5), 1655-1663
- https://doi.org/10.1002/hep.22791
Abstract
We have used immunohistochemical and histochemical techniques to identify patches of hepatocytes deficient in the enzyme cytochrome c oxidase, a component of the electron transport chain and encoded by mitochondrial DNA (mtDNA). These patches invariably abutted the portal tracts and expanded laterally as they spread toward the hepatic veins. Here we investigate, using mtDNA mutations as a marker of clonal expansion, the clonality of these patches. Negative hepatocytes were laser-capture microdissected and mutations identified by polymerase chain reaction sequencing of the entire mtDNA genome. Patches of cytochrome c oxidase–deficient hepatocytes were clonal, suggesting an origin from a long-lived cell, presumably a stem cell. Immunohistochemical analysis of function and proliferation suggested that these mutations in cytochrome c oxidase-deficient hepatocytes were nonpathogenic. Conclusion: these data show, for the first time, that clonal proliferative units exist in the human liver, an origin from a periportal niche is most likely, and that the trajectory of the units is compatible with a migration of cells from the periportal regions to the hepatic veins. (HEPATOLOGY 2009.)Keywords
This publication has 24 references indexed in Scilit:
- Bmi1 is expressed in vivo in intestinal stem cellsNature Genetics, 2008
- Progenitor/stem cells give rise to liver cancer due to aberrant TGF-β and IL-6 signalingProceedings of the National Academy of Sciences of the United States of America, 2008
- Mechanisms of Field Cancerization in the Human Stomach: The Expansion and Spread of Mutated Gastric Stem CellsGastroenterology, 2008
- Hematopoiesis: An Evolving Paradigm for Stem Cell BiologyCell, 2008
- The hepatic stem cell niche: Identification by label-retaining cell assayHepatology, 2008
- Pathophysiology and fate of hepatocytes in a mouse model of mitochondrial hepatopathiesGut, 2007
- Identification of stem cells in small intestine and colon by marker gene Lgr5Nature, 2007
- Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fissionProceedings of the National Academy of Sciences of the United States of America, 2006
- Mitochondrial DNA mutations in human colonic crypt stem cellsJCI Insight, 2003
- Random Intracellular Drift Explains the Clonal Expansion of Mitochondrial DNA Mutations with AgeAmerican Journal of Human Genetics, 2001