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Locating the Stem Cell Niche and Tracing Hepatocyte Lineages in Human Liver

Lookup NU author(s): Professor Doug Turnbull, Professor Robert Taylor, Dr Laura Greaves, Professor Patrick Chinnery

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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;49:1655-1663.)


Publication metadata

Author(s): Fellous TG, Islam S, Tadrous PJ, Elia G, Kocher HM, Bhattacharya S, Mears L, Turnbull DM, Taylor RW, Greaves LC, Chinnery PF, Taylor G, McDonald SAC, Wright NA, Alison MR

Publication type: Article

Publication status: Published

Journal: Hepatology

Year: 2009

Volume: 49

Issue: 5

Pages: 1655-1663

ISSN (print): 0270-9139

ISSN (electronic): 1527-3350

Publisher: John Wiley & Sons, Inc.

URL: http://dx.doi.org/10.1002/hep.22791

DOI: 10.1002/hep.22791


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