Cited by 89Liver physiology and pathologyLiver Disease Diagnosis and TreatmentLiver Diseases and Immunity

Initiation of hepatic stellate cell activation extends into chronic liver disease

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De Smet, Vincent, Eysackers, Nathalie, Merens, Vincent, Kazemzadeh Dastjerd, Mina, Halder, Georg, Verhulst, Stefaan, Mannaerts, Inge, van Grunsven, Leo A.·2021·Cell Death & Disease

Abstract

Activated hepatic stellate cells (aHSC) are the main source of extra cellular matrix in liver fibrosis. Activation is classically divided in two phases: initiation and perpetuation. Currently, HSC-based therapeutic candidates largely focus on targeting the aHSCs in the perpetuation phase. However, the importance of HSC initiation during chronic liver disease (CLD) remains unclear. Here, we identified transcriptional programs of initiating and activated HSCs by RNA sequencing, using in vitro and in vivo mouse models of fibrosis. Importantly, we show that both programs are active in HSCs during murine and human CLD. In human cirrhotic livers, scar associated mesenchymal cells employ both transcriptional programs at the single cell level. Our results indicate that the transcriptional programs that drive the initiation of HSCs are still active in humans suffering from CLD. We conclude that molecules involved in the initiation of HSC activation, or in the maintenance of aHSCs can be considered equally important in the search for druggable targets of chronic liver disease.

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Authors
De Smet, V., Eysackers, N., Merens, V., Kazemzadeh Dastjerd, M., Halder, G., Verhulst, S., Mannaerts, I., & van Grunsven, L. A.
Affiliations
  • Vrije Universiteit Brussel (BE)
  • VIB-KU Leuven Center for Cancer Biology (BE)
Venue
Cell Death & Disease
Published
2021-11-27
Volume
12
Issue
12
Pages
1110-1110
ISSN
2041-4889 (ISSN-L)
OpenAlex
W3216990250
Cited by
78
References
36
Citations by year
2026: 15 · 2025: 24 · 2024: 17 · 2023: 15 · 2022: 6 · 2021: 1
FWCI
6.96
Type
journal article
Language
en
Open access
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lirias (KU Leuven) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • VUBIR (Vrije Universiteit Brussel) (submittedVersion)
Funders
  • Fonds Wetenschappelijk Onderzoek (1192920N, 1243121N, 117300 / 12N5415N LV)
  • Bijzonder Onderzoeksfonds
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Keywords
hepatic stellate cells, chronic liver disease, liver fibrosis, extracellular matrix, transcriptional programs, liver cirrhosis, single-cell RNA sequencing, druggable targets
MeSH terms
Animals, Chronic Disease, Disease Models, Animal, Humans, Liver Diseases, Male, Mice, Hepatic Stellate Cells

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