Transcriptomic profiling of iPSC-derived astrocytes from patients with 22q11.2 deletion syndrome

Abstract

Background: Neurodevelopmental disorders represent considerable public health challenges.One of the syndromes associated with heightened risk of NDDs is 22q11.2 Deletion Syndrome (22q11.2DS), caused by microdeletion in chromosomal region 22q11.2. However, molecular mechanisms underlying NDDs are largely unidentified. Here we analyzed transcriptomic profiling of 22q11.2DS astrocytes. Material and Methods: Total RNA was isolated from iPSCs-derived astrocytes of two cases with familial 22q11.2DS with 1.5Mb microdeletion and one healthy control. Paired- end 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. Results: 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 oligosymptomatic 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. Conclusion: We provide preliminary evidence for an altered transcriptomic landscape of 22q11.2DS astrocytes.Book of absctracts: European Society of Human Genetics (ESHG) 2025 Conference, May 24–27, 2025. Milan, Ital