Cell lineage tracing in the human pancreas :

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Background and aims: The human pancreas is normally proliferatively quiescent; however loss of cells gives a rapid regenerative response to restore a functionally healthy tissue mass. The mechanism for this is unclear and to date research has failed to identify a definitive pancreatic stem cell. Cell lineage analyses are possible in animals by labelling cells with radioactive tags or genetic markers, but this is not feasible in humans. Current human studies rely on stem cell markers, thus there is a need to develop a better technique to track, isolate and identify cells of related origin. Mitochondrial DNA mutations amass naturally within our cells as we age. Therefore, cells formed by division of a stem cell carrying mutated mitochondrial DNA should, given a qualitative assay, permit the progeny of this cell to be traced. Methods and results: Mitochondrial DNA mutations often result in a defect in the mitochondrial DNA-encoded protein cytochrome c oxidase, and can be identified using a histochemical stain. Individual mutant patches were studied by staining serial sections of normal pancreas. This revealed the presence of clonal units of cells, strong evidence that pancreatic cells within each patch are derived from a common progenitor. We tried to show that these cells are normal in synthetic and proliferative function, although this showed that the mitochondrial DNA mutated cells didn’t have normal synthetic function. However this did not negate our evidence of clonal proliferation. Conclusion: This novel means of tracing patterns of cell division and migration in human tissues...