Integrative GWAS and snRNA-seq Reveal a Mesenchymal-Like Endothelial Signature in Moyamoya Disease - PubMed
3 hours ago
- #GWAS
- #Endothelial cells
- #Moyamoya disease
- Moyamoya disease (MMD) has a strong genetic basis, with the rare RNF213 variant (rs112735431) being a major risk factor.
- A genome-wide association study (GWAS) in Japanese individuals identified a significant signal in the HDAC9-TWIST1 region (P=3.3×10^-14; odds ratio, 1.77).
- A protective RNF213 missense variant, p.Asn1331Gly (rs8074015), was found to be mutually exclusive with the rs112735431-A allele.
- Single-nucleus RNA-seq (snRNA-seq) revealed a mesenchymal-like endothelial cell (MEC) population with selective FN1 expression, enriched in MMD.
- MECs showed mesenchymal pathway activation and a distinct regulatory program compared to canonical endothelial states.
- The proportion of MECs was significantly higher in MMD (72%) compared to controls (28%).
- Immunohistochemistry confirmed FN1 expression in endothelial regions of MMD patients.