Single-Cell Analysis Highlights Pivotal Role of Eosinophil-Basophil Mast Cell Progenitor-Related Mechanism in Primary...

Immune thrombocytopenia (ITP) is an autoimmune disease. Megakaryocyte dysfunction caused by autoimmune response can lead to thrombocytopenia, and the underlying mechanism is still unclear. Single-cell sequencing analysis revealed the heterogeneity of CD34 + HSPCs in bone marrow between ITP patients and healthy groups. Pre-B cell population 1 (pre-B1) showed a significantly lower percentage contribution in ITP groups, and the underlying mechanism involves cell cycle-, cell apoptosis- and cell death-related pathways. The number of eosinophil-basophil mast cell progenitors (EBMPs) is significantly increased in ITP patients and the DEGs of the EBMPs in ITP patients were significantly enriched in immune-related pathways. Further, immunofluorescent staining and Western blot assay highlight C-X-C Motif Chemokine Ligand 8 (CXCL8) and Interferon Regulatory Factor 1 (IRF1) expression were significantly increased in the EBMPs of ITP patients. Furthermore, cell-cell communication analysis identified an impaired LGALS9-CD44 axis between EBMP cells and MkP1 cells in ITP patients, suggesting that targeting the LGALS9-CD44 interaction might hold promise as a therapeutic approach for ITP. Our observations indicate that ITP patients exhibit an elevated proportion of EBMP cells alongside a reduced proportion of pre-B1 cells. CXCL8 and IRF1 are potentially associated with EBMP cell dysfunction and the ITP disease process. Furthermore, the diminished LGALS9-CD44 axis between EBMP and MkP1 cells may contribute to ITP progression, suggesting a direction for future therapeutic investigation.