Language
English
Publication Date
11-1-2025
Journal
Blood Vessels, Thrombosis & Hemostasis
DOI
10.1016/j.bvth.2025.100107
PMID
41235340
PMCID
PMC12607065
PubMedCentral® Posted Date
9-10-2025
PubMedCentral® Full Text Version
Post-print
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.
Published Open-Access
yes
Recommended Citation
Lecluze, Estelle; Da Silva Faria, Stennio; Saby, Manon; et al., "Ubiquitous Dysregulation of the Wnt Pathway in Immune Thrombocytopenia Genetic Susceptibility" (2025). Faculty, Staff and Students Publications. 6376.
https://digitalcommons.library.tmc.edu/baylor_docs/6376
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