Single cell RNAseq of peripheral blood mononuclear cells from children with mitochondrial disease

Mitochondria are nearly ubiquitous in all cells, suggesting that mitochondrial dysfunction may extend to the immune system. In this study, we utilized Single-Cell RNA sequencing (scRNA-seq) to characterize cellular heterogeneity and the pathologic underpinnings of mitochondrial disease in peripheral blood mononuclear cells from pediatric patients. Transcriptomes of individual cells from affected and healthy tissue samples revealed marked reductions in select populations involved in the humoral immune response, especially antigen presenting cells, B cell and plasma populations, with sparing of T cell populations. MTRNR2L8, a marker of bioenergetic stress, was significantly elevated in populations that were most depleted. mir4485, a miRNA contained in the intron of MTRNR2L8, was co-expressed. mir4485 was found to have a role in promoting survival by modulating apoptosis. The results highlight distinct molecular phenotypes and identify previously unrecognized in mitochondrial diseases. Case-control single cell RNAseq contributor: NISC Comparative Sequencing Program >>>Submitter states: Raw data not available due to patient privacy concerns. Raw data will be submitted to dbGaP.<<<