Study on FSHD2 Myotube Nucleus Disease Based on Mononuclear RNA-seq Identification

Abstract

Facioscapulohumeral Muscular Dystrophy (FSHD) is a genetic disease that leads to progressively wasting of facial, shoulder, and upper arm musculature. We performed a PCA analysis on the bulk RNA-seq datasets to observe the variances in gene expression profiles that could distinguish the impacts of genotypes and myoblast differentiation. We found out that the variance of differentiation (51.9%) was much higher than the percentage of variance of genotype difference (5.9%). Corresponding to this, we also found that only a small portion of differentially expressed genes were driven by the FSHD effect only, and the vast rest were driven by differentiation effect. These results further confirmed the difficulties in detecting FSHD induced or DUX4 downstream genes from bulk RNA-seq datasets and highlighted our downstream analysis by using a single-nucleus RNA-seq dataset to dissect the pathology in disease-associated populations.