ArticleCell death & disease2021
PU.1 drives specification of pluripotent stem cell-derived endothelial cells to LSEC-like cells.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- The Scavenger Function of LSECs, a Regulator of Liver Diseases.Current issues in molecular biology · 2026Review
- Periodontitis and MASLD: a narrative review of the direct oral-hepatic pathway.Frontiers in cellular and infection microbiology · 2026Review
- Loss of endothelial ZEB2 in mice attenuates steatosis early during metabolic dysfunction-associated steatotic liver disease.Scientific reports · 2025Article
- Identification of Cell Fate Determining Transcription Factors for Generating Brain Endothelial Cells.Stem cell reviews and reports · 2025Article
- A streamlined method to generate endothelial cells from human pluripotent stem cells via transient doxycycline-inducible ETV2 activation.Angiogenesis · 2024Article
- A novel efficient strategy to generate liver sinusoidal endothelial cells from human pluripotent stem cells.Scientific reports · 2024Article
- Liver specification of human iPSC-derived endothelial cells transplanted into mouse liver.JHEP reports : innovation in hepatology · 2024Article
- Publication characteristics and visualized analysis of research about liver sinusoidal endothelial cells.iLIVER · 2024Article
- Exploring the Molecular and Developmental Dynamics of Endothelial Cell Differentiation.International journal of stem cells · 2024Review
- Osmolar Modulation Drives Reversible Cell Cycle Exit and Human Pluripotent Cell Differentiation via NF-κВ and WNT Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Spatially Self-Organized Three-Dimensional Neural Concentroid as a Novel Reductionist Humanized Model to Study Neurovascular Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Transcriptional regulation of the HIV-1 inhibitory factor human mannose receptor 1 by the myeloid-specific transcription factor PU.1.Journal of virology · 2024Article
- Generation of functional liver sinusoidal endothelial-like cells from human bone marrow-derived mesenchymal stem cells.Regenerative therapy · 2023Article
- Liver endothelial cells in NAFLD and transition to NASH and HCC.Cellular and molecular life sciences : CMLS · 2023Review
- Review
- Advancements in MAFLD Modeling with Human Cell and Organoid Models.International journal of molecular sciences · 2022Review
- The Myeloid-Specific Transcription Factor PU.1 Upregulates Mannose Receptor Expression but Represses Basal Activity of the HIV-LTR Promoter.Journal of virology · 2022Article
- Current Status and Challenges of Human Induced Pluripotent Stem Cell-Derived Liver Models in Drug Discovery.Cells · 2022Review
- Organ-Specific Endothelial Cell Differentiation and Impact of Microenvironmental Cues on Endothelial Heterogeneity.International journal of molecular sciences · 2022Review
- Ficolin-2: A potential immune-related therapeutic target with low expression in liver cancer.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To date, there is no representative in vitro model for liver sinusoidal endothelial cells (LSECs), as primary LSECs dedifferentiate very fast in culture and no combination of cytokines or growth factors can induce an LSEC fate in (pluripotent stem cell (PSC)-derived) endothelial cells (ECs). Furthermore, the transcriptional programmes driving an LSEC fate have not yet been described. Here, we first present a computational workflow (CenTFinder) that can identify transcription factors (TFs) that are crucial for modulating pathways involved in cell lineage specification. Using CenTFinder, we identified several novel LSEC-specific protein markers, such as FCN2 and FCN3, which were validated by analysis of previously published single-cell RNAseq data. We also identified PU.1 (encoded by the SPI1 gene) as a major regulator of LSEC-specific immune functions. We show that SPI1 overexpression (combined with the general EC TF ETV2) in human PSCs induces ECs with an LSEC-like phenotype. The ETV2-SPI1-ECs display increased expression of LSEC markers, such as CD32B and MRC1, as well as several of the proposed novel markers. More importantly, ETV2-SPI1-ECs acquire LSEC functions, including uptake of FSA-FITC, as well as labelled IgG. In conclusion, we present the CenTFinder computational tool to identify key regulatory TFs within specific pathways, in this work pathways of lineage specification, and we demonstrate its use by the identification and validation of PU.1 as a master regulator for LSEC fating.
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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.