ArticleScience advances2022
DLL4 and VCAM1 enhance the emergence of T cell-competent hematopoietic progenitors from human pluripotent stem cells.
Article in Science advances, 2022. 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, 41 citations in OpenAlex.
- Allogeneic iPSC-derived γδT cells demonstrate antitumor efficacy against patient-derived tissues.Stem cell reports · 2026Article
- Feeder-free generation of functional dendritic cells from human pluripotent stem cells.Journal for immunotherapy of cancer · 2026Article
- Advancing adoptive cellular immunotherapy via Notch-based ex vivo T cell development platforms.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Review
- Human Progenitor T-Cell Differentiation Regulated by the Mechanical Resistance of Thymus-Mimetic Extracellular Matrices.Advanced healthcare materials · 2026Article
- Regulatory T cell therapies: biological foundations, engineering strategies, and clinical translation.Frontiers in immunology · 2026Review
- ThymUS approaching maturity.Nature immunology · 2025Article
- Protocol for the generation of HLF+ HOXA+ human hematopoietic progenitor cells from pluripotent stem cells.STAR protocols · 2025Article
- Pluripotent stem cell-based immunotherapy: advances in translational research, cell differentiation, and gene modifications.Life medicine · 2025Review
- Gene-level alignment of single-cell trajectories.Nature methods · 2025Article
- Role of the Notch ligand DLL4 in the immune response of children with Mycoplasma pneumoniae pneumonia.Revista do Instituto de Medicina Tropical de Sao Paulo · 2025Article
- Optimizing in vitro T cell differentiation by using induced pluripotent stem cells with GFP-RUNX1 and mCherry-TCF7 labelling.Cell proliferation · 2024Article
- Accelerating Diverse Cell-Based Therapies Through Scalable Design.Annual review of chemical and biomolecular engineering · 2024Review
- Lineage-tracing hematopoietic stem cell origins in vivo to efficiently make human HLF+ HOXA+ hematopoietic progenitors from pluripotent stem cells.Developmental cell · 2024Article
- Unlocking the potential of iPSC-derived immune cells: engineering iNK and iT cells for cutting-edge immunotherapy.Frontiers in immunology · 2024Review
- New tricks for an old pathway: emerging Notch-based biotechnologies and therapeutics.Trends in pharmacological sciences · 2023Review
- The genesis of human hematopoietic stem cells.Blood · 2023Article
- Lymphoid cell development from fetal hematopoietic progenitors and human pluripotent stem cells.Immunological reviews · 2023Review
- Engineering T Cell Development for the Next Generation of Stem Cell-Derived Immunotherapies.GEN biotechnology · 2023Review
- 'Off the shelf' immunotherapies: Generation and application of pluripotent stem cell-derived immune cells.Cell proliferation · 2023Review
- Organs-on-a-chip: a union of tissue engineering and microfabrication.Trends in biotechnology · 2023Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cells show tremendous efficacy as cellular therapeutics. However, obtaining primary T cells from human donors is expensive and variable. Pluripotent stem cells (PSCs) have the potential to provide a renewable source of T cells, but differentiating PSCs into hematopoietic progenitors with T cell potential remains an important challenge. Here, we report an efficient serum- and feeder-free system for differentiating human PSCs into hematopoietic progenitors and T cells. This fully defined approach allowed us to study the impact of individual proteins on blood emergence and differentiation. Providing DLL4 and VCAM1 during the endothelial-to-hematopoietic transition enhanced downstream progenitor T cell output by ~80-fold. These two proteins synergized to activate notch signaling in nascent hematopoietic stem and progenitor cells, and VCAM1 additionally promoted an inflammatory transcriptional program. We also established optimized medium formulations that enabled efficient and chemically defined maturation of functional CD8αβ
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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.