ArticleLeukemia2015
The Notch ligand DLL4 specifically marks human hematoendothelial progenitors and regulates their hematopoietic fate.
Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
- ABlood vessels, thrombosis & hemostasis · 2025Article
- Single-Chain Nanobody Inhibition of Notch and Avidity Enhancement Utilizing the β-Pore-Forming Toxin Aerolysin.ACS chemical biology · 2025Article
- Single-chain nanobody inhibition of Notch and avidity enhancement utilizing the β-pore forming toxin Aerolysin.bioRxiv : the preprint server for biology · 2024Article
- Cis inhibition of NOTCH1 through JAGGED1 sustains embryonic hematopoietic stem cell fate.Nature communications · 2024Article
- MicroRNA-223 limits murine hemogenic endothelial cell specification and myelopoiesis.Developmental cell · 2023Article
- Review
- The long and winding road: homeostatic and disordered haematopoietic microenvironmental niches: a narrative review.Biomaterials translational · 2022Review
- Regulation of Hemogenic Endothelial Cell Development and Function.Annual review of physiology · 2021Review
- A splicing factor switch controls hematopoietic lineage specification of pluripotent stem cells.EMBO reports · 2021Article
- The RUNX1b Isoform Defines Hemogenic Competency in Developing Human Endothelial Cells.Frontiers in cell and developmental biology · 2021Article
- A Benchmark Side-by-Side Comparison of Two Well-Established Protocols forFrontiers in cell and developmental biology · 2021Article
- Arterial endothelium creates a permissive niche for expansion of human cord blood hematopoietic stem and progenitor cells.Stem cell research & therapy · 2020Article
- MSX2 suppression through inhibition of TGFβ signaling enhances hematopoietic differentiation of human embryonic stem cells.Stem cell research & therapy · 2020Article
- IL-7R is essential for leukemia-initiating cell activity of T-cell acute lymphoblastic leukemia.Blood · 2019Article
- Notch1 signaling in NOTCH1-mutated mantle cell lymphoma depends on Delta-Like ligand 4 and is a potential target for specific antibody therapy.Journal of experimental & clinical cancer research : CR · 2019Article
- GATA2 Promotes Hematopoietic Development and Represses Cardiac Differentiation of Human Mesoderm.Stem cell reports · 2019Article
- Enhanced hemato-endothelial specification during human embryonic differentiation through developmental cooperation betweenHaematologica · 2019Article
- MEIS2 regulates endothelial to hematopoietic transition of human embryonic stem cells by targeting TAL1.Stem cell research & therapy · 2018Article
- Early Human Hemogenic Endothelium Generates Primitive and Definitive Hematopoiesis In Vitro.Stem cell reports · 2018Article
- The NOTCH1/CD44 axis drives pathogenesis in a T cell acute lymphoblastic leukemia model.The Journal of clinical investigation · 2018Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch signaling is essential for definitive hematopoiesis, but its role in human embryonic hematopoiesis is largely unknown. We show that in hESCs the expression of the Notch ligand DLL4 is induced during hematopoietic differentiation. We found that DLL4 is only expressed in a sub-population of bipotent hematoendothelial progenitors (HEPs) and segregates their hematopoietic versus endothelial potential. We demonstrate at the clonal level and through transcriptome analyses that DLL4(high) HEPs are enriched in endothelial potential, whereas DLL4(low/-) HEPs are committed to the hematopoietic lineage, albeit both populations still contain bipotent cells. Moreover, DLL4 stimulation enhances hematopoietic differentiation of HEPs and increases the amount of clonogenic hematopoietic progenitors. Confocal microscopy analysis of whole differentiating embryoid bodies revealed that DLL4(high) HEPs are located close to DLL4(low/-) HEPs, and at the base of clusters of CD45+ cells, resembling intra-aortic hematopoietic clusters found in mouse embryos. We propose a model for human embryonic hematopoiesis in which DLL4(low/-) cells within hemogenic endothelium receive Notch-activating signals from DLL4(high) cells, resulting in an endothelial-to-hematopoietic transition and their differentiation into CD45+ hematopoietic cells.
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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.