ArticleBlood2021
Immune cells surveil aberrantly sialylated O-glycans on megakaryocytes to regulate platelet count.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Glycosylation orchestrates megakaryocytic fate of hematopoietic stem cells via Wnt-MUC13 signaling.Nature communications · 2026Article
- Nascent preplatelets and B4GALT1 glycosylation contribute to 5-FU-induced bone marrow recovery.Blood advances · 2026Article
- The glycan fingerprint in immune thrombocytopenia.Research and practice in thrombosis and haemostasis · 2026Article
- Stratified assessment of platelets in sepsis: from dynamic counts to functional phenotypes.Frontiers in immunology · 2026Review
- Single-cell transcriptomics reveals an abnormal immune microenvironment in plasma cell mastitis.Annals of medicine · 2025Article
- Spatial Transcriptional Dynamics of CD74⁺ B Cells in Tertiary Lymphoid Structures Drive Immune Evolution in Penile Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- High-Dimensional Spatiotemporal Single-Cell and 3D Atlas of the Bone Marrow Microenvironment during Leukemic Progression.bioRxiv : the preprint server for biology · 2025Article
- Differently expressed miRNA in plasma samples of immune thrombocytopenic purpura patients and its clinical significance.Journal of medical biochemistry · 2025Article
- New insights into the generation and function of megakaryocytes in health and disease.Haematologica · 2025Review
- Single-Cell Sequencing Reveals PD-L1-Mediated Immune Escape Signaling in Lung Adenocarcinoma.Journal of Cancer · 2025Article
- Genetic variants in canonical Wnt signaling pathway associated with pediatric immune thrombocytopenia.Blood advances · 2024Article
- The role of plasmacytoid dendritic cells (pDCs) in immunity during viral infections and beyond.Cellular & molecular immunology · 2024Review
- IFIT3 mediates TBK1 phosphorylation to promote activation of pDCs and exacerbate systemic sclerosis in mice.Clinical and translational medicine · 2024Article
- Sialic acid in the regulation of blood cell production, differentiation and turnover.Immunology · 2024Review
- Article
- Pathogenesis of refractory ITP: Overview.British journal of haematology · 2023Review
- Inside-to-outside and back to the future of megakaryopoiesis.Research and practice in thrombosis and haemostasis · 2023Article
- Comprehensive analysis of platelet glycoprotein Ibα ectodomain glycosylation.Journal of thrombosis and haemostasis : JTH · 2023Article
- Inherited Thrombocytopenia Caused by Variants in Crucial Genes for Glycosylation.International journal of molecular sciences · 2023Review
- Circulating immune cells with megakaryocyte signature in response to COVID-19 mRNA vaccination.Thrombosis research · 2022Article
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Immune thrombocytopenia (ITP) is a platelet disorder. Pediatric and adult ITP have been associated with sialic acid alterations, but the pathophysiology of ITP remains elusive, and ITP is often a diagnosis of exclusion. Our analysis of pediatric ITP plasma samples showed increased anti-Thomsen-Friedenreich antigen (TF antigen) antibody representation, suggesting increased exposure of the typically sialylated and cryptic TF antigen in these patients. The O-glycan sialyltransferase St3gal1 adds sialic acid specifically on the TF antigen. To understand if TF antigen exposure associates with thrombocytopenia, we generated a mouse model with targeted deletion of St3gal1 in megakaryocytes (MK) (St3gal1MK-/-). TF antigen exposure was restricted to MKs and resulted in thrombocytopenia. Deletion of Jak3 in St3gal1MK-/- mice normalized platelet counts implicating involvement of immune cells. Interferon-producing Siglec H-positive bone marrow (BM) immune cells engaged with O-glycan sialic acid moieties to regulate type I interferon secretion and platelet release (thrombopoiesis), as evidenced by partially normalized platelet count following inhibition of interferon and Siglec H receptors. Single-cell RNA-sequencing determined that TF antigen exposure by MKs primed St3gal1MK-/- BM immune cells to release type I interferon. Single-cell RNA-sequencing further revealed a new population of immune cells with a plasmacytoid dendritic cell-like signature and concomitant upregulation of the immunoglobulin rearrangement gene transcripts Igkc and Ighm, suggesting additional immune regulatory mechanisms. Thus, aberrant TF antigen moieties, often found in pathological conditions, regulate immune cells and thrombopoiesis in the BM, leading to reduced platelet count.
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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.