CSF1R modulates megakaryopoiesis by targeting RUNX1 in immune thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by platelet destruction and defective megakaryopoiesis. However, the mechanisms underlying megakaryocyte (MK) dysfunction in ITP remain unclear. To address this, we performed single-cell RNA sequencing (scRNA-seq) on bone marrow cells from a newly diagnosed ITP patient. ScRNA-seq analysis revealed a marked upregulation of colony-stimulating factor 1 receptor (CSF1R) in MK compared with healthy control. This finding was independently validated by flow cytometry in additional clinical samples. In vitro, MK differentiation and maturation were significantly impaired in ITP, and these defects were rescued by inhibition of CSF1R. In an active murine model of ITP, CSF1R inhibition accelerated platelet recovery. Mechanistically, elevated CSF1R expression suppressed the transcription factor RUNX1, a key regulator of megakaryopoiesis. In conclusion, our findings identify CSF1R as a previously unrecognized regulator of megakaryopoiesis and suggest it represents a promising therapeutic target in ITP.