Multimodal single-cell analysis of nonrandom heteroplasmy distribution in human retinal mitochondrial disease.

ABSTRACT: Variants within the high copy number mitochondrial genome (mtDNA) can disrupt organelle function and lead to severe multisystem disease. The wide range of manifestations observed in patients with mitochondrial disease results from varying fractions of abnormal mtDNA molecules in different cells and tissues, a phenomenon termed heteroplasmy. However, the landscape of heteroplasmy across cell types within tissues and its influence on phenotype expression in affected patients remains largely unexplored. Here, we identify nonrandom distribution of a pathogenic mtDNA variant across a complex tissue using single-cell RNA-Seq, mitochondrial single-cell ATAC sequencing, and multimodal single-cell sequencing. We profiled the transcriptome, chromatin accessibility state, and heteroplasmy in cells fr

SUBMITTER: Mullin NK 

PROVIDER: S-EPMC10443808 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature