ArticleScience immunology2022
Notch-dependent cooperativity between myeloid lineages promotes Langerhans cell histiocytosis pathology.
Article in Science immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Article
- Histiocytosis development and clinical variation through the lens of genomics.The Journal of pathology · 2026Review
- Pre-diagnostic metabolites in peripheral blood of Langerhans cell histiocytosis children with posterior pituitary involvement.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Single-cell and spatial transcriptome analysis reveals the potential therapeutic targets for testicular sex cord-stromal cell tumor.Biomarker research · 2026Article
- DC subsets and states unraveled across human juxtatumoral and malignant tissues.Nature immunology · 2026Article
- Histiocyte Society blueprint for Langerhans cell histiocytosis research: from cell-of-origin to a more comprehensive cure.Haematologica · 2025Review
- [Immune microenvironment of Langerhans cell histiocytosis: from immune suppression to targeted therapy].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Review
- BRAFV600E induces key features of LCH in iPSCs with cell type-specific phenotypes and drug responses.Blood · 2025Article
- Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity.Science immunology · 2024Article
- Intestinal stroma guides monocyte differentiation to macrophages through GM-CSF.Nature communications · 2024Article
- Identification and characterization of stromal-like cells with CD207BMC cancer · 2024Article
- BRAFLeukemia · 2023Article
- Langerhans cell histiocytosis: current advances in molecular pathogenesis.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
37 authors at 9 institutions in 7 countries.
Funding
Abstract
Langerhans cell histiocytosis (LCH) is a potentially fatal neoplasm characterized by the aberrant differentiation of mononuclear phagocytes, driven by mitogen-activated protein kinase (MAPK) pathway activation. LCH cells may trigger destructive pathology yet remain in a precarious state finely balanced between apoptosis and survival, supported by a unique inflammatory milieu. The interactions that maintain this state are not well known and may offer targets for intervention. Here, we used single-cell RNA-seq and protein analysis to dissect LCH lesions, assessing LCH cell heterogeneity and comparing LCH cells with normal mononuclear phagocytes within lesions. We found LCH discriminatory signatures pointing to senescence and escape from tumor immune surveillance. We also uncovered two major lineages of LCH with DC2- and DC3/monocyte-like phenotypes and validated them in multiple pathological tissue sites by high-content imaging. Receptor-ligand analyses and lineage tracing in vitro revealed Notch-dependent cooperativity between DC2 and DC3/monocyte lineages during expression of the pathognomonic LCH program. Our results present a convergent dual origin model of LCH with MAPK pathway activation occurring before fate commitment to DC2 and DC3/monocyte lineages and Notch-dependent cooperativity between lineages driving the development of LCH cells.
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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.