Clonal Dynamics And Cell-Of-Origin Of Normal Hepatocyte Expansions In Homeostatic Human Livers And Their Association With The Biliary Epithelium

In high turnover epithelial tissues such as the intestine, homeostatic cellular replacement is achieved via a pool of stem cells. By contrast, turnover in the normal human liver is slow and the location and necessity of liver stem cells has been hotly debated. Partial hepatectomy has demonstrated that new hepatocytes can be generated from pre-existing hepatocytes, without the requirement of a stem cell population. However, lineage tracing in chronic injury models supports the involvement of liver stem/progenitors. Further complexity has arisen from the demonstration of both periportal and centrilobular neo-hepatocyte generation. This collective knowledge has largely amassed from rodent studies such that far less is known regarding the dynamics of human liver turnover, particularly during normal homeostasis. We have explored hepatocyte expansion dynamics in normal human liver by marking mitochondrial …