ArticleBlood advances2023
An in vitro model of human hematopoiesis identifies a regulatory role for the aryl hydrocarbon receptor.
Article in Blood advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Cannabidiol and ΔToxicology · 2026Article
- From animal models to NAMs: a paradigm shift in developmental immunotoxicity testing.Archives of toxicology · 2026Review
- Single-cell transcriptomics reveals a differential response of human bronchial epithelial cell-types to cadmium chloride.Archives of toxicology · 2026Article
- Aryl hydrocarbon receptor activation alters emergency hematopoiesis during influenza A virus infection.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- HIDmap: a physiology-based map of human immune system development to support animal-free research and regulatory innovation.Frontiers in immunology · 2026Article
- Assessment of immunotoxicity in the 21st century: Where we are and what we need to replace animals.Current opinion in toxicology · 2025Article
- Regulation of in vitro human hematopoietic differentiation by dioxin-like compounds.Toxicology · 2025Article
- Using the Key Characteristics Framework to Unlock the Mysteries of Aryl Hydrocarbon Receptor-Mediated Effects on the Immune System.Annual review of immunology · 2025Review
- Role of the Aryl Hydrocarbon Receptor in the Self-Renewal, Differentiation, and Immunomodulation of Adult Stem Cells.Immune network · 2025Review
- CD9 and Aryl Hydrocarbon Receptor Are Markers of Human CD19+CD14+ Atypical B Cells and Are Dysregulated in Systemic Lupus Erythematous Disease.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Application of Single Cell Methods in Immunometabolism and Immunotoxicology.Current opinion in toxicology · 2024Article
- Unique challenges and best practices for single cell transcriptomic analysis in toxicology.Current opinion in toxicology · 2024Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
In vitro models to study simultaneous development of different human immune cells and hematopoietic lineages are lacking. We identified and characterized, using single-cell methods, an in vitro stromal cell-free culture system of human hematopoietic stem and progenitor cell (HSPC) differentiation that allows concurrent development of multiple immune cell lineages. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor influencing many biological processes in diverse cell types. Using this in vitro model, we found that AHR activation by the highly specific AHR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin, drives differentiation of human umbilical cord blood-derived CD34+ HSPCs toward monocytes and granulocytes with a significant decrease in lymphoid and megakaryocyte lineage specification that may lead to reduced immune competence. To our knowledge, we also discovered for the first time, using single-cell modalities, that AHR activation decreased the expression of BCL11A and IRF8 in progenitor cells, which are critical genes involved in hematopoietic lineage specification processes at both transcriptomic and protein levels. Our in vitro model of hematopoiesis, coupled with single-cell tools, therefore allows for a better understanding of the role played by AHR in modulating hematopoietic differentiation.
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Registered trials
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