GENE EXPRESSION PROFILING OF ASTROCYTES DERIVED FROM IPSCS OF PATIENTS WITH 22Q11.2 DELETION SYNDROME

Abstract

Deletion Syndrome (22q11.2DS), caused by microdeletion 22q11.2, is the most common microdeletion syndrome in humans. t is closely linked to an increased risk of neurodevelopmental disorders and provides a valuable model for investigating the molecular mechanisms underlying these disorders, which are still not fully understood. Here we analyzed transcriptomic profiling of 22q11.2DS astrocytes derived from iPSCs of mother and child with 22q11.2DS and one healthy control. RNA-seq was carried out on Illumina NovaSeq 6000 sequencer. Bioinformatic processing of raw data was conducted via NVIDIA platform, while differential gene expression analysis was performed in RStudio using DESeq2 R package. The obtained list of DEGs was used for pathway enrichment analysis by employing EnrichR and WikiPathways. 125 DEGs with lower expression and 287 DEGs with higher expression in 22q11.2DS astrocytes compared to the control were obtained. For genes with lower expression in 22q11.2DS astrocytes, 22q11.2 Copy Number Variation Syndrome and Axon Guidance were the top enriched pathways, while for genes with higher expression in 22q11.2DS astrocytes we did not identify biological pathways that are enriched in DEG lists more than would be expected by chance. We found 178 DEGs with lower expression and 205 DEGs with higher expression in astrocytes of symptomatic child with 22q11.2DS compared to non-symptomatic mother with 22q11.2DS. Employing EnrichR and WikiPathways we did not identify biological pathways that are enriched in DEG lists more than would be expected by chance. Our findings offer preliminary evidence of an altered transcriptomic landscape of 22q11.2DS astrocytes.Abstract book: FENS Regional Meeting 2025, Oslo, Norway, 16-19 June 202