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Cited by 57Liver physiology and pathologyBarrier Structure and Function StudiesGenomics and Chromatin Dynamics

Unraveling the transcriptional determinants of liver sinusoidal endothelial cell specialization

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de Haan, Willeke, Øie, Cristina, Benkheil, Mohammed, Dheedene, Wouter, Vinckier, Stefan, Coppiello, Giulia, Aranguren, Xabier López, Beerens, Manu +5 more·2020·American Journal of Physiology-Gastrointestinal and Liver Physiology
DOI 10.1152/ajpgi.00215.2019PMC PMC7191457
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Abstract

Liver sinusoidal endothelial cells (LSECs) are the first liver cells to encounter waste macromolecules, pathogens, and toxins in the blood and are highly specialized. Although some transcription factors are known to play a role in LSEC specialization, information about the specialized LSEC signature and its transcriptional determinants remains incomplete. Here, we show that C-MAF, GATA4, and MEIS2 are important transcriptional regulators of the unique LSEC signature and that they affect the interaction of LSECs with viruses.

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  • SCENIC+ analysis revealed 180 eRegulons, including SPI1, JDP2, RUNX1 in Kupffer cells; EBF1 and PAX5 in B cells; GATA3 and LEF1 in T cells; GATA4, MEIS1 and MAF in LSECs; LHX2 and TEAD1 in HSCs; WT1 in fibroblasts; and TEAD4, DOX4 and HNF1B in BECs, among others, in agreement with literature.

    “This analysis revealed 180 eRegulons, including SPI1, JDP2, RUNX1 in Kupffer cells; EBF1 and PAX5 in B cells; GATA3 and LEF1 in T cells; GATA4, MEIS1 and MAF in LSECs; LHX2 and TEAD1 in HSCs; WT1 in fibroblasts; and TEAD4, DOX4 and HNF1B in BECs, among others, and in agreement with literature15–20.”

    From Single-cell spatial multi-omics and deep learning dissect enhancer-driven gene regulatory networks in liver zonation (2024) · cites this paper as [18]

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  • This approach identified PU.1, Runx, and Irf as candidate TFs for Kupffer cell enhancers; Pax5 and Ebf1 for B cells; Tbx21 for T cells; Meis1, Maf and Gata4 for LSECs; Mef2c and Lhx2 for HSC; and Tead4, Sox9 and Hnf1b for BECs.

    “this approach identified PU.1, Runx, and Irf as candidate TFs for Kupffer cell enhancers37; Pax5 and Ebf1 for B cells38; Tbx21 for T cells39; Meis1, Maf and Gata4 for LSECs40; Mef2c and Lhx2 for HSC41; and Tead4, Sox9 and Hnf1b for BECs42”

    From Enhancer grammar of liver cell types and hepatocyte zonation states (2022) · cites this paper as [40]

    The Results (p. 4) identify C-MAF, GATA4, and MEIS2 as regulators of LSEC marker expression, supporting the LSEC attribution for Maf and Gata4. The cited paper identifies MEIS2, not Meis1, and tests marker expression after TF overexpression rather than identifying candidates for LSEC enhancers. (LLM, conf=0.91)

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Sorted by citations

Authors
de Haan, W., Øie, C., Benkheil, M., Dheedene, W., Vinckier, S., Coppiello, G., Aranguren, X. L., Beerens, M., Jaekers, J., Topal, B., Verfaillie, C., Smedsrød, B., & Luttun, A.
Affiliations
  • Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
  • UiT The Arctic University of Norway (NO)
  • Rega Institute for Medical Research (BE)
  • KU Leuven (BE)
  • Vlaams Instituut voor Biotechnologie (BE)
  • Universitair Ziekenhuis Leuven (BE)
Corresponding author
Luttun, Aernout
ORCID
Venue
American Journal of Physiology-Gastrointestinal and Liver Physiology
Publisher
American Physiological Society
Published
2020-04-01
Volume
318
Issue
4
Pages
G803-G815
ISSN
  • 0193-1857 (ISSN-L)
  • 1522-1547
DOI
10.1152/ajpgi.00215.2019
PMC
PMC7191457
OpenAlex
W3010018628
Cited by
57
References
2
Citations by year
2026: 5 · 2025: 9 · 2024: 7 · 2023: 11 · 2022: 11 · 2021: 14
FWCI
5.29
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Lirias (submittedVersion, other-oa)
Funders
  • EC | European Research Council (FP7-StG-IMAGINED203291)
  • Cosmetics Europe/ European commission FP7 (FP7-Health-HemiBio266777)
  • KU Leuven Program Financing (PF/10/014)
  • Interuniversity attraction poles (IUAP/P7/07)
  • Marie Sklodowska-Curie (H2020-MSCA-IF-REZONABLE658666)
  • FWO (1157318N)
  • IWT (SB/0881071)
  • KU Leuven C1 competitive funding (C14/19/095, C12/16/023)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
liver sinusoidal endothelial cells, transcriptional regulation, c-Maf, GATA4, MEIS2, transcription factors, viral infection, liver endothelium
MeSH terms
Animals, Gene Expression Regulation, Genetic Markers, Humans, Liver, Male, Organ Specificity, Endothelial Cells, Rats, Transcriptome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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