Blood Vessel Thromb Hemost. 2025 Sep 10;2(4):100107. doi: 10.1016/j.bvth.2025.100107. eCollection 2025 Nov.
ABSTRACT
The pathogenesis of immune thrombocytopenia (ITP) is complex and incompletely understood. Multiple cell types have been implicated, and their respective contribution is unclear. A recent genome-wide association study identified single-nucleotide polymorphisms (SNPs) associated with pediatric ITP within or near 5 genes in the canonical Wnt signaling pathway. To investigate whether this pathway was dysregulated in ITP and identify which cell types were involved, we leveraged extensive functional genomics and single-cell RNA sequencing (scRNA-seq) data. By linking the identified SNPs to likely regulated genes, we showed an enrichment in the Wnt pathway and identified 2 additional genes in this pathway involved in ITP. The SNPs affected regulation of the Wnt pathway genes in multiple cell types. Indeed, scRNA-seq showed some of these genes were expressed in lymphocytes, whereas others were expressed in platelets or megakaryocytes. By comparing the cell-specific expression of these genes between individuals with ITP and healthy controls, we demonstrated that several genes in the Wnt pathway were differentially expressed between these 2 groups. Some genes were upregulated, whereas other were downregulated in ITP. In sum, the Wnt signaling pathway is broadly dysregulated in ITP, with a complex pattern that varies across genes and cell types.
PMID:41235340 | PMC:PMC12607065 | DOI:10.1016/j.bvth.2025.100107
