Mitochondrial variant enrichment from high-throughput single-cell RNA sequencing resolves clonal populations

The combination of single-cell transcriptomics with mitochondrial DNA variant detection can be used to establish lineage relationships in primary human cells, but current methods are not scalable to interrogate complex tissues. Here, we combine common 3' single-cell RNA-sequencing protocols with mitochondrial transcriptome enrichment to increase coverage by more than 50-fold, enabling high-confidence mutation detection. The method successfully identifies skewed immune-cell expansions in primary human clonal hematopoiesis.

Automated summary

The combination of single-cell transcriptomics and mitochondrial DNA variant detection is useful for establishing lineage relationships in primary human cells, but current methods are not suitable for analyzing complex tissues. In this study, researchers combined common 3' single-cell RNA-sequencing protocols with mitochondrial transcriptome enrichment to significantly increase coverage and enable high-confidence mutation detection. This method successfully identified skewed immune cell expansions in primary human clonal hematopoiesis.