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Cited by 109Liver physiology and pathologyAngiogenesis and VEGF in CancerBarrier Structure and Function Studies

Liver sinusoidal endothelium: a microenvironment-dependent differentiation program in rat including the novel junctional protein liver endothelial differentiation-associated protein-1

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Géraud, Cyrill, Schledzewski, Kai, Demory, Alexandra, Klein, Diana, Kaus, Miriam, Peyre, Francis, Sticht, Carsten, Evdokimov, Konstantin +3 more·2010·Hepatology
DOI 10.1002/hep.23618
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Abstract

Liver sinusoidal endothelium (LSEC) is a prime example of organ-specific microvascular differentiation and functions. Disease-associated capillarization of LSEC in vivo and dedifferentiation of LSEC in vitro indicate the importance of the hepatic microenvironment. To identify the LSEC-specific molecular differentiation program in the rat we used a two-sided gene expression profiling approach comparing LSEC freshly isolated ex vivo with both lung microvascular endothelial cells (LMEC) and with LSEC cultured for 42 hours. The LSEC signature consisted of 48 genes both down-regulated in LMEC and in LSEC upon culture (fold change >7 in at least one comparison); quantitative reverse-transcription polymerase chain reaction confirmation of these genes included numerous family members and signaling pathway-associated molecules. The LSEC differentiation program comprised distinct sets of growth (Wnt2, Fzd4, 5, 9, Wls, vascular endothelial growth factors [VEGFR] 1, 2, 3, Nrp2) and transcription factors (Gata4, Lmo3, Tcfec, Maf) as well as endocytosis-related (Stabilin-1/2, Lyve1, and Ehd3) and cytoskeleton-associated molecules (Rnd3/RhoE). Specific gene induction in cultured LSEC versus freshly isolated LSEC as well as LMEC (Esm-1, Aatf) and up-regulation of gene expression to LMEC levels (CXCR4, Apelin) confirmed true transdifferentiation of LSEC in vitro . In addition, our analysis identified a novel 26-kDa single-pass transmembrane protein, liver endothelial differentiation-associated protein (Leda)-1, that was selectively expressed in all liver endothelial cells and preferentially localized to the abluminal cell surface. Upon forced overexpression in MDCK cells, Leda-1 was sorted basolaterally to E-cadherin-positive adherens junctions, suggesting functional involvement in cell adhesion and polarity. Conclusion: Comparative microvascular analysis in rat identified a hepatic microenvironment-dependent LSEC-specific differentiation program including the novel junctional molecule Leda-1. Hepatology 2010

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  • Early HSECs express transcription factors associated with sinusoidal identity, such as Sox17, Tfec, Maf, and Dab2.

    “early HSECs express transcription factors associated with sinusoidal identity, such as Sox17, Tfec, Maf, and Dab2”

    From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Géraud et al., 2010

    The section on the LSEC differentiation program identifies Tfec and Maf as LSEC-specific transcription factors, supporting those two examples. The paper examines freshly isolated rat LSECs rather than early HSECs, and the passages found do not identify Sox17 or Dab2 as sinusoidal-identity transcription factors. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The early HSEC transcriptome suggests the activation of sinusoidal function, including endocytosis, antigen presentation, and signaling.

    “the early HSEC transcriptome further suggests the activation of sinusoidal function, including endocytosis (Stab2, Colec12, Ehd3, and Lyve1), antigen presentation (Fcgrt, Fcer1g, and Mrc1), and signaling (Gpr182, Bmp2, Dll4, and Efna1)”

    From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Géraud et al., 2010

    The section on the microenvironment-dependent LSEC program (page unavailable) identifies endocytosis, immune-system processes, and cytokine/growth-factor signaling among its gene clusters; Table 1 lists Ehd3, Stabilin-2, and Bmp2. But the paper profiles freshly isolated rat LSECs and their changes in culture, not an early HSEC transcriptome, and the cited passages do not establish the full set of genes or antigen-presentation activity in that early setting. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • These factors are not enriched within the HSEC trajectory where instead, beginning as early as E8.75, HSEC-specific transcription factors are activated, including Tfec, Nr5a2, Sox17, and Oit3, as well as genes associated with HSEC identity, including Stab2, Lyve1, and Fcgrt.

    “These factors are not enriched within the HSEC trajectory where instead, beginning as early as E8.75, HSEC-specific transcription factors are activated, including Tfec, Nr5a2, Sox17, and Oit3, as well as genes associated with HSEC identity, including Stab2, Lyve1, and Fcgrt”

    From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Géraud et al., 2010

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

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Authors
Géraud, C., Schledzewski, K., Demory, A., Klein, D., Kaus, M., Peyre, F., Sticht, C., Evdokimov, K., Lu, S., Schmieder, A., & Goerdt, S.
Affiliations
Heidelberg University (DE)
Corresponding author
Géraud, Cyrill
ORCID
Venue
Hepatology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2010-07
Volume
52
Issue
1
Pages
313-326
ISSN
0270-9139 (ISSN-L)
DOI
10.1002/hep.23618
OpenAlex
W1984564880
Cited by
109
References
1
Citations by year
2026: 2 · 2025: 4 · 2024: 8 · 2023: 5 · 2022: 11 · 2021: 7 · 2020: 18 · 2019: 5 · 2018: 8 · 2017: 9 · 2016: 6 · 2015: 9 · 2014: 7 · 2013: 3 · 2012: 2
FWCI
1.87
Type
journal article
Language
en
Open access
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 1888 d)
Locations
  • Hepatology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (GRK880, Project B1, Project 3)
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
liver sinusoidal endothelium, endothelial differentiation, hepatic microenvironment, adherens junctions, cell adhesion, cell polarity, transdifferentiation, dedifferentiation, capillarization, gene expression profiling, lung microvascular endothelial cells, Wnt signaling, VEGF receptors, GATA4, E-cadherin, basolateral sorting
MeSH terms
Animals, Capillaries, Cell Differentiation, Cell Line, Dogs, Endocytosis, Endothelium, Vascular, Genetic Markers, Liver, Membrane Proteins, Transcription Factors, Rats, Sprague-Dawley, Gene Expression Profiling, Adherens Junctions, Receptors, Vascular Endothelial Growth Factor, Rats

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