ArticleBlood2014
Blood stem cell fate regulation by Delta-1-mediated rewiring of IL-6 paracrine signaling.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Ex-vivo Expansion of Cord Blood Hematopoietic Stem Cells in Serum-Free Medium with Feeder Layer - A New Hope for Successful Cord Blood Transplantation in Adults.International journal of hematology-oncology and stem cell research · 2025Article
- Expression of extracellular matrix components in the meibomian gland.Frontiers in medicine · 2022Article
- Multilevel defects in the hematopoietic niche in essential thrombocythemia.Haematologica · 2020Article
- Notch signaling mitigates chemotherapy toxicity by accelerating hematopoietic stem cells proliferation via c-Myc.American journal of translational research · 2020Article
- Interleukin-6 signaling regulates hematopoietic stem cell emergence.Experimental & molecular medicine · 2019Article
- Integration of T-cell receptor, Notch and cytokine signals programs mouse γδ T-cell effector differentiation.Immunology and cell biology · 2018Article
- Progenitor T-cell differentiation from hematopoietic stem cells using Delta-like-4 and VCAM-1.Nature methods · 2017Article
- Regulating dynamic signaling between hematopoietic stem cells and niche cells via a hydrogel matrix.Biomaterials · 2017Article
- Endothelial Cells Promote Expansion of Long-Term Engrafting Marrow Hematopoietic Stem and Progenitor Cells in Primates.Stem cells translational medicine · 2017Article
- Notch Signaling in the Regulation of Hematopoietic Stem Cell.Current stem cell reports · 2017Review
- Challenges and Opportunities to Harnessing the (Hematopoietic) Stem Cell Niche.Current stem cell reports · 2016Article
- Endothelium-targeted human Delta-like 1 enhances the regeneration and homing of human cord blood stem and progenitor cells.Journal of translational medicine · 2016Article
- How to Improve Cord Blood Engraftment?Frontiers in medicine · 2016Review
- Intercellular network structure and regulatory motifs in the human hematopoietic system.Molecular systems biology · 2014Article
- Notch and human hematopoietic stem cells.Blood · 2014Article
- Delta-1 provides pleasant stem cell environs.Blood · 2014Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Increasing evidence supports the importance of cell extrinsic regulation in stem cell fate control. Hematopoietic stem cells (HSC) are responsive to local signals from their niche and to systemic feedback from progenitors and mature cells. The Notch ligand Delta-1 (DL1), a key component of the stem cell niche, regulates human hematopoietic lineage development in a dose-dependent manner and has been used clinically for primitive progenitor expansion. How DL1 acts to regulate HSC fate and whether these actions are related to its lineage skewing effects are poorly understood. Here we demonstrate that, although DL1 activates signal transducer and activator of transcription 3 signaling similarly to the gp130-activating cytokine interleukin-6 (IL-6), it has opposite effects on myeloid cell production. Mechanistically, these different outcomes are attributable to a DL1-mediated reduction in membrane (m)-bound IL-6 receptor (R) expression, converting progenitor cells from being directly IL-6 responsive to requiring both IL-6 and soluble (s) IL-6R for activation. Concomitant reduction of both mIL-6R (by DL1 supplementation) and sIL-6R (using dynamically fed cultures) reduced myeloid cell production and led to enhanced outputs of human HSCs. This work describes a new mode of cytokine action in which DL1 changes cytokine receptor distributions on hematopoietic cells, altering feedback networks and their impact on stem cell fate.
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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.