Evidence map›Paper›PMID 34588551›Full record

ArticleScientific reports2021

Single-cell and bulk transcriptomics of the liver reveals potential targets of NASH with fibrosis.

Zhong-Yi Wang, Adrian Keogh, Annick Waldt, Rachel Cuttat, Marilisa Neri, Shanshan Zhu, Sven Schuierer, Alexandra Ruchti, Christophe Crochemore, Judith Knehr and 9 more

Abstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
–field-weighted citation impact
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

83 citing papers in PubMed.

  1. Article
  2. Precision pathophysiology in steatotic liver disease.Clinical and molecular hepatology · 2026
    Review
  3. Gene-Based Clustering Identifies QSOX1 and IL1RAP as Biomarkers of Metabolic Dysfunction-Associated Steatotic Liver Disease.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Article
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  7. Review
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23 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

19 authors.

Zhong-Yi WangNovartis Institutes for BioMedical Research, 4056, Basel, Switzerland. zhongyi.wang@novartis.com.
Adrian KeoghVisceral Surgery and Medicine, Inselspital, Bern University Hospital, Department for BioMedical Research, University of Bern, 3008, Bern, Switzerland.
Annick WaldtNovartis Institutes for BioMedical Research, 4056, Basel, Switzerland.
Rachel CuttatNovartis Institutes for BioMedical Research, 4056, Basel, Switzerland.
Marilisa NeriNovartis Institutes for BioMedical Research, 4056, Basel, Switzerland.
Shanshan ZhuChina Novartis Institutes for BioMedical Research, Shanghai, 201203, China.
Sven SchuiererNovartis Institutes for BioMedical Research, 4056, Basel, Switzerland.
Alexandra RuchtiNovartis Institutes for BioMedical Research, 4056, Basel, Switzerland.
Christophe CrochemoreNovartis Institutes for BioMedical Research, 4056, Basel, Switzerland.
Judith KnehrNovartis Institutes for BioMedical Research, 4056, Basel, Switzerland.
Julie BastienNovartis Institutes for BioMedical Research, 4056, Basel, Switzerland.
Iwona KsiazekNovartis Institutes for BioMedical Research, 4056, Basel, Switzerland.
Daniel Sánchez-TaltavullVisceral Surgery and Medicine, Inselspital, Bern University Hospital, Department for BioMedical Research, University of Bern, 3008, Bern, Switzerland.
Hui GeChina Novartis Institutes for BioMedical Research, Shanghai, 201203, China.
Jing WuChina Novartis Institutes for BioMedical Research, Shanghai, 201203, China.
Guglielmo RomaNovartis Institutes for BioMedical Research, 4056, Basel, Switzerland.
Stephen B HelliwellNovartis Institutes for BioMedical Research, 4056, Basel, Switzerland.
Deborah StrokaVisceral Surgery and Medicine, Inselspital, Bern University Hospital, Department for BioMedical Research, University of Bern, 3008, Bern, Switzerland.
Florian NigschNovartis Institutes for BioMedical Research, 4056, Basel, Switzerland. florian.nigsch@novartis.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fibrosis is characterized by the excessive production of collagen and other extracellular matrix (ECM) components and represents a leading cause of morbidity and mortality worldwide. Previous studies of nonalcoholic steatohepatitis (NASH) with fibrosis were largely restricted to bulk transcriptome profiles. Thus, our understanding of this disease is limited by an incomplete characterization of liver cell types in general and hepatic stellate cells (HSCs) in particular, given that activated HSCs are the major hepatic fibrogenic cell population. To help fill this gap, we profiled 17,810 non-parenchymal cells derived from six healthy human livers. In conjunction with public single-cell data of fibrotic/cirrhotic human livers, these profiles enable the identification of potential intercellular signaling axes (e.g., ITGAV-LAMC1, TNFRSF11B-VWF and NOTCH2-DLL4) and master regulators (e.g., RUNX1 and CREB3L1) responsible for the activation of HSCs during fibrogenesis. Bulk RNA-seq data of NASH patient livers and rodent models for liver fibrosis of diverse etiologies allowed us to evaluate the translatability of candidate therapeutic targets for NASH-related fibrosis. We identified 61 liver fibrosis-associated genes (e.g., AEBP1, PRRX1 and LARP6) that may serve as a repertoire of translatable drug target candidates. Consistent with the above regulon results, gene regulatory network analysis allowed the identification of CREB3L1 as a master regulator of many of the 61 genes. Together, this study highlights potential cell-cell interactions and master regulators that underlie HSC activation and reveals genes that may represent prospective hallmark signatures for liver fibrosis.

Indexed as

Hepatic Stellate CellsNon-alcoholic Fatty Liver DiseaseTranscriptomeAnimalsHealthy VolunteersHumansRatsSingle-Cell Analysis

Identifiers

PMID34588551
PMCPMC8481490

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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.