ArticleScience (New York, N.Y.)2021
Liver homeostasis is maintained by midlobular zone 2 hepatocytes.
Article in Science (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 132 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
132 citing papers in PubMed, 273 citations in OpenAlex.
- Inhibiting cyclin D1-CDK6 suppresses senescence-associated inflammatory gene expression and age-related functional decline.Nature aging · 2026Article
- Solute Carrier Family 1 Member 5 (SLC1A5)-dependent glutamine transport regulates macrophage senescence and efferocytosis during liver regeneration.Molecular biomedicine · 2026Article
- Haemodynamic control of zonated liver function via instructive vascular Wnt signalling.Nature communications · 2026Article
- Alcohol reshapes liver zonal plasticity and immune-metabolic reprogramming in metabolic-syndrome associated hepatocellular carcinoma.Nature communications · 2026Article
- From Collapse to Active Self-Repair: Integrative Multi-Omics and Machine Learning Analysis Map the Hepatic Metabolic Adaption in Response to Simulated Spaceflight Stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- SPACE-seq integrates spatial transcriptomics and lineage tracing in native tissues.Cell stem cell · 2026Article
- Single-cell and spatial omics in liver identify cell-cell communication regulators in aging and insulin resistance.Metabolism: clinical and experimental · 2026Article
- Hepatocyte hedgehog signaling controls ferroptosis to alleviate aging-related organ dysfunction.JCI insight · 2026Article
- Single-cell spatial transcriptomics reveals hepatocyte reprogramming in Fontan-associated liver disease.JCI insight · 2026Article
- Spatial hepatology: Decoding liver zonation for metabolic and regenerative therapeutics (Review).International journal of molecular medicine · 2026Review
- SpNeigh: spatial neighborhood and differential expression analysis for high-resolution spatial transcriptomics.NAR genomics and bioinformatics · 2026Article
- Glutathione peroxidase 3 preserves hepatocyte mitochondrial quality control to enhance macrophage pro-regenerative phenotype during liver regeneration.Clinical and translational medicine · 2026Article
- Spatial profiling of gene editing by in situ sequencing in mice and macaques.Nature biomedical engineering · 2026Article
- In vivo dynamics of G-quadruplex DNA structures during liver regeneration in mice.Scientific reports · 2026Article
- Chronic psychological stress disrupts liver homeostasis by dysregulating oxidative phosphorylation via the PI3K/AKT/FoxO3a axis.iScience · 2026Article
- Signal control during tissue regeneration in adult animals.Nature reviews. Molecular cell biology · 2026Review
- Rumen Mycobiome Thiamine Metabolism Contributes to Subacute Rumen Acidosis Tolerance in Goats Through Enhancing Epithelial Cell Proliferation via IGFBP2/IGF1 Axis Activation.Exploration (Beijing, China) · 2026Article
- Lipid-dependent accrual of a subset of monocyte-derived macrophages is essential for tissue regeneration.Nature metabolism · 2026Article
- Conversion of Transplanted Mature Hepatocytes into AfpAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The origin of hepatocellular carcinoma depends on metabolic zonation.Science (New York, N.Y.) · 2026Article
72 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
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- Erratum issued
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
The liver is organized into zones in which hepatocytes express different metabolic enzymes. The cells most responsible for liver repopulation and regeneration remain undefined, because fate mapping has only been performed on a few hepatocyte subsets. Here, 14 murine fate-mapping strains were used to systematically compare distinct subsets of hepatocytes. During homeostasis, cells from both periportal zone 1 and pericentral zone 3 contracted in number, whereas cells from midlobular zone 2 expanded in number. Cells within zone 2, which are sheltered from common injuries, also contributed to regeneration after pericentral and periportal injuries. Repopulation from zone 2 was driven by the insulin-like growth factor binding protein 2-mechanistic target of rapamycin-cyclin D1 (IGFBP2-mTOR-CCND1) axis. Therefore, different regions of the lobule exhibit differences in their contribution to hepatocyte turnover, and zone 2 is an important source of new hepatocytes during homeostasis and regeneration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.