Broad Distribution of Hepatocyte Proliferation in Liver Homeostasis and Regeneration

Autor: Khushbu Sharma, Ajay Ravindranathan, Feng Chen, Bradley A. Stohr, Hubert Y. Luu, Holger Willenbring, Bernadette Y. Hsu, Robert J. Jimenez
Rok vydání: 2020
Předmět:
liver stem cells
1.1 Normal biological development and functioning
Chronic Liver Disease and Cirrhosis
Population
Liver Stem Cell
clonal expansion
Biology
liver
Regenerative Medicine
Medical and Health Sciences
Oral and gastrointestinal
Article
lineage tracing
Underpinning research
homeostasis
hepatocyte
Genetics
medicine
Lobules of liver
liver regeneration
education
Cell Proliferation
education.field_of_study
5.2 Cellular and gene therapies
Liver Disease
Regeneration (biology)
Wnt signaling pathway
ploidy
Cell Biology
Biological Sciences
Stem Cell Research
Liver regeneration
Cell biology
medicine.anatomical_structure
regeneration
Hepatocyte
Hepatocytes
Molecular Medicine
Stem Cell Research - Nonembryonic - Non-Human
liver zonation
Development of treatments and therapeutic interventions
Stem cell
Digestive Diseases
Developmental Biology
Zdroj: Cell Stem Cell
Cell stem cell, vol 26, iss 1
ISSN: 1934-5909
DOI: 10.1016/j.stem.2019.11.001
Popis: Hepatocyte proliferation is the principal mechanism for generating new hepatocytes in liver homeostasis and regeneration. Recent studies have suggested that this ability is not equally distributed among hepatocytes but concentrated in a small subset of hepatocytes acting like stem cells, located around the central vein or distributed throughout the liver lobule and exhibiting active WNT signaling or high telomerase activity, respectively. These findings were obtained by utilizing components of these growth regulators as markers for genetic lineage tracing. Here, we used random lineage tracing to localize and quantify clonal expansion of hepatocytes in normal and injured liver. We found that modest proliferation of hepatocytes distributed throughout the lobule maintains the hepatocyte mass and that most hepatocytes proliferate to regenerate it, with diploidy providing a growth advantage over polyploidy. These results show that the ability to proliferate is broadly distributed among hepatocytes rather than limited to a rare stem cell-like population.
Databáze: OpenAIRE
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