Evidence map›Paper›PMID 34792289›Full record

ArticleHepatology communications2022

Single-Cell, Single-Nucleus, and Spatial RNA Sequencing of the Human Liver Identifies Cholangiocyte and Mesenchymal Heterogeneity.

Tallulah S Andrews, Jawairia Atif, Jeff C Liu, Catia T Perciani, Xue-Zhong Ma, Cornelia Thoeni, Michal Slyper, Gökcen Eraslan, Asa Segerstolpe, Justin Manuel and 10 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Hepatology communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers.

0numbers the graph read from it
0cells of the map it votes in
191citing papers in PubMed
19.2field-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

191 citing papers in PubMed, 266 citations in OpenAlex.

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  9. Precision pathophysiology in steatotic liver disease.Clinical and molecular hepatology · 2026
    Review
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  11. Review
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  14. Article
  15. Review
  16. Review
  17. Article
  18. Liver Macrophages in the Pathogenesis of Viral Hepatitis.Current issues in molecular biology · 2026
    Review
  19. Review
  20. Article

131 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

20 authors at 3 institutions in 2 countries.

Tallulah S Andrews *Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
Jawairia Atif *Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
Jeff C Liu *Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Catia T PercianiAjmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
Xue-Zhong MaAjmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
Cornelia ThoeniDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Michal SlyperKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Gökcen EraslanKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Asa SegerstolpeKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Justin ManuelAjmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
Sai ChungAjmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
Erin WinterAjmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
Iulia CirlanPrincess Margaret Genome Centre, University Health Network, Toronto, ON, Canada.
Nicholas KhuuPrincess Margaret Genome Centre, University Health Network, Toronto, ON, Canada.
Sandra FischerDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Orit Rozenblatt-RosenKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Aviv RegevKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Ian D McGilvrayAjmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
Gary D BaderDepartment of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Sonya A MacParlandAjmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.ORCID 0000-0002-8036-1425
University Health Network · CABroad Institute · USUniversity of Toronto · CA

Funding

TR&D 3 - Network Guided Machine LearningP41GM103504 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2012 to 2024
$17.3M
Cytoscape: A Modeling Platform for Biomolecular NetworksR01HG009979 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2017 to 2021
$3.5M
NHGRI NIH HHS R01 HG009979NIGMS NIH HHS P41 GM103504
6 · The paper itself

Abstract

The critical functions of the human liver are coordinated through the interactions of hepatic parenchymal and non-parenchymal cells. Recent advances in single-cell transcriptional approaches have enabled an examination of the human liver with unprecedented resolution. However, dissociation-related cell perturbation can limit the ability to fully capture the human liver's parenchymal cell fraction, which limits the ability to comprehensively profile this organ. Here, we report the transcriptional landscape of 73,295 cells from the human liver using matched single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq). The addition of snRNA-seq enabled the characterization of interzonal hepatocytes at a single-cell resolution, revealed the presence of rare subtypes of liver mesenchymal cells, and facilitated the detection of cholangiocyte progenitors that had only been observed during in vitro differentiation experiments. However, T and B lymphocytes and natural killer cells were only distinguishable using scRNA-seq, highlighting the importance of applying both technologies to obtain a complete map of tissue-resident cell types. We validated the distinct spatial distribution of the hepatocyte, cholangiocyte, and mesenchymal cell populations by an independent spatial transcriptomics data set and immunohistochemistry. Conclusion: Our study provides a systematic comparison of the transcriptomes captured by scRNA-seq and snRNA-seq and delivers a high-resolution map of the parenchymal cell populations in the healthy human liver.

Indexed as

LiverSingle-Cell AnalysisCell NucleusHumansSequence Analysis, RNATranscriptome

Identifiers

PMID34792289
PMCPMC8948611
OpenAlexW3213918788

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.