Trisomy 21 is the most common chromosomal disorder and underlies Down syndrome. Epigenetics, such as DNA methylation and post-translational histone modifications, plays a vital role in Down syndrome. However, the functions of epigenetics-related long noncoding RNAs (lncRNAs), found to have an impact on neural diseases such as Alzheimer’s disease, remain unknown in Down syndrome.
In this study, researchers from Shanghai Jiao Tong University School of Medicine analyzed the RNA sequencing data from Down syndrome-induced pluripotent stem cells (iPSCs) and normal iPSCs. A large number of lncRNAs were identified differentially expressed in Down syndrome-iPSCs. Notably, stronger perturbation was shown in the expression of lncRNAs compared to protein coding genes (Kolmogorov-Smirnov test, P <0.05), suggesting that lncRNAs play more important roles in Down syndrome. Through gene set enrichment analysis and bi-clustering, the researchers also found that most of the differential expressed lncRNAs were closely associated with mitochondrial functions. PCR-array and qRT-PCR results revealed that almost all genes related to mitochondria were down-regulated in Down syndrome-iPSCs, implying that mitochondria were dysfunctional in Down syndrome. All in all, this study indicated that a stronger perturbation of lncRNAs expression may lead to the dysfunction of mitochondria in Down syndrome.
Expression-based association matrix for 582 lncRNAs (rows) and functional gene sets (columns) derived from gene set enrichment analysis. Red indicates a positive correlation,blue indicates a negative correlation, and white indicates no correlation. Rows correspond to lncRNAs that were differentially expressed in DS-iPSCs compared with Normal-iPSCs. The area within the green box indicates Bicluster_3.