GENE EXPRESSION PROFILING OF IPSC-DERIVED NEURAL PROGENITORS FROM PATIENTS WITH 22Q11.2 DUPLICATION SYNDROME

Abstract

The molecular mechanisms underlying neurodevelopmental disorders (NDDs) are understudied. 22q11.2 Duplication Syndrome (22q11.2DupS) is associated with an increased risk of NDDs, including autism spectrum disorders, developmental delay, and intellectual disability, while potentially having protective effect against schizophrenia. Here we performed transcriptomic profiling of 22q11.2DupS neural progenitors (NPCs). Total RNA was isolated from iPSCs-derived NPCs of a family trio consisting of a child with 22q11.2DupS, a carrier unaffected mother, and a healthy control father. Paired-end RNA-sequencing was carried out by commercial services. FASTQ files were processed on an NVIDIA platform and differential gene expression analysis was carried out in RStudio using the DESeq2 R package. The resulting lists of differentially expressed genes (DEGs) was utilized for pathway and gene ontology enrichment analysis using clusterProfiler in RStudio. 60 DEGs with lower expression and 58 DEGs with higher expression were obtained in 22q11.2DupS NPCs compared to both carrier and control NPCs. For genes with lower expression in 22q11.2DupS NPCs, “miRNA targets in ECM and membrane receptors” was the top enriched pathway. On the other hand, for genes with higher expression in 22q11.2DupS NPCs, no biological pathways were identified as being significantly enriched in the DEG list beyond what would be expected by chance. However, for genes with higher expression in 22q11.2DupS NPCs, we obtained statistically significant enrichment of molecular functions such as Histone demethylase activity. 22q11.2DupS NPCs exhibit altered signaling pathways and molecular functions, providing preliminary insights into the impact of this microduplication on neural differentiation.Abstract book: FENS Regional Meeting 2025, Oslo, Norway, 16-19 June 202