Mutations in the huntingtin gene (HTT) on chromosome 4 leading to repetition of CAG codon more than 36 times (mHTT) will result in autosomal dominant Huntington’s disease (HD). mHTT protein not only disrupts the gene regulation of mitochondrial function-related proteins, but also affects microtubules, mitochondrial dynamic fusion and division, and calcium transport. In this research, we aimed to investigate the cellular pathways affected by mHTT in in vitro models of HD.

To address this aim, we re-analyzed publicly available single-cell RNA-Seq (scRNA-Seq) dataset from neuroloids derived from patients with and without HD previously published by Haremaki et al. (2019) in Nature. The normalized count matrix provided by authors was re-analyzed using Seurat package in RStudio, the data were integrated, filtered and differentially expressed genes between control cells and cell derived from patients with HD were plotted. The results were compared with other publicly available scRNA-Seq datasets.

The use of scRNA-Seq datasets and in vitro models of HD allows us to compare single cell gene expressions from specific cell types of interest. The gene expression differences between neuroloids derived from HD and control patients may help to identify the effects of mHTT mutation, shedding the light on the cellular pathways affected in HD.