Evidence map›Paper›PMID 34027339›Full record

ArticleJHEP reports : innovation in hepatology2021

Single-cell RNA sequencing of human liver reveals hepatic stellate cell heterogeneity.

Valéry L Payen, Arnaud Lavergne, Niki Alevra Sarika, Megan Colonval, Latifa Karim, Manon Deckers, Mustapha Najimi, Wouter Coppieters, Benoît Charloteaux, Etienne M Sokal and 1 more

Open access · goldAbstract read
In one paragraph

Article in JHEP reports : innovation in hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed, 1 pooled it
11.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

105 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Actin cytoskeletal dynamics in hepatic myofibroblasts and fibrosis.Nature reviews. Gastroenterology & hepatology · 2026
    Review
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  9. Organism-scale annotation with Pan-human Azimuth.bioRxiv : the preprint server for biology · 2026
    Article
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  20. Purification and Transcriptomic Characterization of Hypertrophied Hepatic Stellate Cells From CDAHFD Mouse Liver.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article

45 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Valéry L PayenLaboratory of Pediatric Hepatology and Cell Therapy (PEDI), IREC Institute, Université catholique de Louvain, Brussels, Belgium.
Arnaud LavergneGenomics Platform, GIGA Institute, Université de Liège, Liège, Belgium.
Niki Alevra SarikaLaboratory of Pediatric Hepatology and Cell Therapy (PEDI), IREC Institute, Université catholique de Louvain, Brussels, Belgium.
Megan ColonvalGenomics Platform, GIGA Institute, Université de Liège, Liège, Belgium.
Latifa KarimGenomics Platform, GIGA Institute, Université de Liège, Liège, Belgium.
Manon DeckersGenomics Platform, GIGA Institute, Université de Liège, Liège, Belgium.
Mustapha NajimiLaboratory of Pediatric Hepatology and Cell Therapy (PEDI), IREC Institute, Université catholique de Louvain, Brussels, Belgium.
Wouter CoppietersGenomics Platform, GIGA Institute, Université de Liège, Liège, Belgium.
Benoît CharloteauxGenomics Platform, GIGA Institute, Université de Liège, Liège, Belgium.
Etienne M SokalLaboratory of Pediatric Hepatology and Cell Therapy (PEDI), IREC Institute, Université catholique de Louvain, Brussels, Belgium.
Adil El TaghdouiniLaboratory of Pediatric Hepatology and Cell Therapy (PEDI), IREC Institute, Université catholique de Louvain, Brussels, Belgium.
University of Liège · BEUCLouvain · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsThe multiple vital functions of the human liver are performed by highly specialised parenchymal and non-parenchymal cells organised in complex collaborative sinusoidal units. Although crucial for homeostasis, the cellular make-up of the human liver remains to be fully elucidated. Here, single-cell RNA-sequencing was used to unravel the heterogeneity of human liver cells, in particular of hepatocytes (HEPs) and hepatic stellate cells (HSCs).

methodThe transcriptome of ~25,000 freshly isolated human liver cells was profiled using droplet-based RNA-sequencing. Recently published data sets and RNA

resultsIn total, 22 cell populations were annotated that reflected the heterogeneity of human parenchymal and non-parenchymal liver cells. More than 20,000 HEPs were ordered along the portocentral axis to confirm known, and reveal previously undescribed, zonated liver functions. The existence of 2 subpopulations of human HSCs with unique gene expression signatures and distinct intralobular localisation was revealed (

conclusionsThis study highlights metabolic zonation as a key determinant of HEP transcriptomic heterogeneity and, for the first time, outlines the existence of heterogeneous HSC subpopulations in the human liver. These findings call for further research on the functional implications of liver cell heterogeneity in health and disease. LAY SUMMARY: This study resolves the cellular landscape of the human liver in an unbiased manner and at high resolution to provide new insights into human liver cell biology. The results highlight the physiological heterogeneity of human hepatic stellate cells.

Indexed as

BSA, bovine serum albuminCC, cholangiocyteCV, central veinDEG, differentially expressed geneEC, endothelial cellECM, extracellular matrixExtracellular matrixFFPE, formaldehyde-fixed paraffin embeddedGAG, glycosaminoglycanGEO, Gene Expression OmnibusGO, gene ontologyHepatocyteHEP, hepatocyteHLA, human leukocyte antigenHRP, horseradish peroxidaseHSC, hepatic stellate cellISH, in situ hybridisationKLR, killer lectin-like receptorLiver cell atlasLP, lymphoid cellMP, macrophageMZ, midzonalPC, pericentralPP, periportalPV, portal veinscRNA-seq, single-cell RNA-sequencingTBS, Tris buffered salineTSA, tyramide signal amplificationUMAP, uniform manifold approximation and projectionUMI, unique molecular identifierVIM, vimentinZonation

Identifiers

PMID34027339
PMCPMC8121977
OpenAlexW3136060713

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.