ArticleBlood2022
Endothelial MEKK3-KLF2/4 signaling integrates inflammatory and hemodynamic signals during definitive hematopoiesis.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Cerebral cavernous malformations: epidemiology, molecular pathogenesis, diagnosis and therapy.Molecular biomedicine · 2026Review
- Inhibition of MEKK3 Prevents Cerebral Cavernous Malformation Progression Via Restoring Endothelial Integrity and Restricting Microglial Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Human stem cell models in cerebral cavernous malformations.Stem cell research & therapy · 2026Review
- Hemodynamics in heart: the critical role of hemodynamics in myocardial tissue development and regenerative remodeling.International journal of cardiology. Heart & vasculature · 2026Review
- MEKK3 bridges gut-brain communication and cerebral cavernous malformation pathogenesis.Cell death discovery · 2026Review
- Genotype-integrated single-cell transcriptome analysis reveals the role of DDX41 pR525H in a patient with myelodysplastic neoplasms.Scientific reports · 2025Article
- Endothelial heterogeneity in bone marrow: insights across development, adult life and leukemia.Leukemia · 2025Review
- Unraveling hematopoietic stem cell ontogeny through single-cell multi-omics approaches.Frontiers in cell and developmental biology · 2025Review
- Ribosome biogenesis is essential for hemogenic endothelial cells to generate hematopoietic stem cells.Development (Cambridge, England) · 2024Article
- New insights into the endothelial origin of hematopoietic system inspired by "TIF" approaches.Blood science (Baltimore, Md.) · 2024Review
- MDMA targets miR-124/MEKK3 via MALAT1 to promote Parkinson's disease progression.Molecular biology reports · 2023Article
- Single-Cell RNA-seq Analysis of a Human Embryonic Stem Cell to Endothelial Cell System Based on Transcription Factor Overexpression.Stem cell reviews and reports · 2023Article
- CD82 expression marks the endothelium to hematopoietic transition at the onset of blood specification in human.iScience · 2023Article
- KLF2 is a clinical diagnostic and treatment biomarker of breast cancer.Frontiers in cell and developmental biology · 2023Article
- miRNA-let7b5p alleviates visceral hypersensitivity by inhibiting the activation of spinal microglial in male IBS-like rats.Molecular painArticle
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 4 countries.
Funding
Abstract
The hematopoietic stem cells (HSCs) that produce blood for the lifetime of an animal arise from RUNX1+ hemogenic endothelial cells (HECs) in the embryonic vasculature through a process of endothelial-to-hematopoietic transition (EHT). Studies have identified inflammatory mediators and fluid shear forces as critical environmental stimuli for EHT, raising the question of how such diverse inputs are integrated to drive HEC specification. Endothelial cell MEKK3-KLF2/4 signaling can be activated by both fluid shear forces and inflammatory mediators, and it plays roles in cardiovascular development and disease that have been linked to both stimuli. Here we demonstrate that MEKK3 and KLF2/4 are required in endothelial cells for the specification of RUNX1+ HECs in both the yolk sac and dorsal aorta of the mouse embryo and for their transition to intraaortic hematopoietic cluster (IAHC) cells. The inflammatory mediators lipopolysaccharide and interferon-γ increase RUNX1+ HECs in an MEKK3-dependent manner. Maternal administration of catecholamines that stimulate embryo cardiac function and accelerate yolk sac vascular remodeling increases EHT by wild-type but not MEKK3-deficient endothelium. These findings identify MEKK-KLF2/4 signaling as an essential pathway for EHT and provide a molecular basis for the integration of diverse environmental inputs, such as inflammatory mediators and hemodynamic forces, during definitive hematopoiesis.
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Registered trials
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.