ArticleCellular and molecular gastroenterology and hepatology2020
Transcriptomic Dissection of Hepatocyte Heterogeneity: Linking Ploidy, Zonation, and Stem/Progenitor Cell Characteristics.
Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Isolation of Mononucleated and Binucleated Hepatocytes by Flow Cytometry.Bio-protocol · 2026Article
- Urolithin A activates mitophagy via the AMPK-mTOR axis and modulates the gut-ceramide axis to ameliorate cardiac remodeling in HFpEF.Experimental & molecular medicine · 2026Article
- Spatial hepatology: Decoding liver zonation for metabolic and regenerative therapeutics (Review).International journal of molecular medicine · 2026Review
- Affinity Proteomics-Based Non-Invasive Detection of Clinically Significant Liver Disease.Alimentary pharmacology & therapeutics · 2026Observational
- Integrating the Study of Polyploidy Across Organisms, Tissues, and Disease.Annual review of genetics · 2024Review
- Aberrant differentiation and proliferation of hepatocytes in chronic liver injury and liver tumors.Pathology international · 2024Review
- The Ploidy State as a Determinant of Hepatocyte Proliferation.Seminars in liver disease · 2023Review
- Gene-regulation modules in nonalcoholic fatty liver disease revealed by single-nucleus ATAC-seq.Life science alliance · 2023Article
- Evidence for in vitro extensive proliferation of adult hepatocytes and biliary epithelial cells.Stem cell reports · 2023Article
- Evidence forbioRxiv : the preprint server for biology · 2023Article
- IL6 supports long-term expansion of hepatocytes in vitro.Nature communications · 2022Article
- Tubular cell polyploidy protects from lethal acute kidney injury but promotes consequent chronic kidney disease.Nature communications · 2022Article
- Polyploidy and Myc Proto-Oncogenes Promote Stress Adaptation via Epigenetic Plasticity and Gene Regulatory Network Rewiring.International journal of molecular sciences · 2022Review
- Binucleation ramps up gene expression meeting the physiological demands of an organism.PLoS biology · 2022Article
- Polyploidy as a Fundamental Phenomenon in Evolution, Development, Adaptation and Diseases.International journal of molecular sciences · 2022Review
- Preparation of Functional Human Hepatocytes Ex Vivo.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Review
- Polyploidy in Tissue Repair and Regeneration.Cold Spring Harbor perspectives in biology · 2021Review
- Single-nucleus RNA-seq2 reveals functional crosstalk between liver zonation and ploidy.Nature communications · 2021Article
- Differential Roles for Diploid and Polyploid Hepatocytes in Acute and Chronic Liver Injury.Seminars in liver disease · 2021Review
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsThere is a long-standing debate regarding the biological significance of polyploidy in hepatocytes. Recent studies have provided increasing evidence that hepatocytes with different ploidy statuses behave differently in a context-dependent manner (eg, susceptibility to oncogenesis, regenerative ability after injury, and in vitro proliferative capacity). However, their overall transcriptomic differences in a physiological context is not known.
methodsBy using microarray transcriptome analysis, we investigated the heterogeneity of hepatocyte populations with different ploidy statuses. Moreover, by using single-cell quantitative reverse-transcription polymerase chain reaction (scPCR) analysis, we investigated the intrapopulational transcriptome heterogeneity of 2c and 4c hepatocytes.
resultsMicroarray analysis showed that cell cycle-related genes were enriched in 8c hepatocytes, which is in line with the established notion that polyploidy is formed via cell division failure. Surprisingly, in contrast to the general consensus that 2c hepatocytes reside in the periportal region, in our bulk transcriptome and scPCR analyses, the 2c hepatocytes consistently showed pericentral hepatocyte-enriched characteristics. In addition, scPCR analysis identified a subpopulation within the 2c hepatocytes that co-express the liver progenitor cell markers Axin2, Prom1, and Lgr5, implying the potential biological relevance of this subpopulation.
conclusionsThis study provides new insights into hepatocyte heterogeneity, namely 2c hepatocytes are preferentially localized to the pericentral region, and a subpopulation of 2c hepatocytes show liver progenitor cell-like features in terms of liver progenitor cell marker expression (Axin2, Prom1, and Lgr5).
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