Genome

Single cell sequencing

Cell

Transcriptome

Mitochondrial DNA

Biology

Gene

Deep sequencing

Gene expression

Mutation

DNA sequencing

Computational biology

Exome sequencing

Single-cell analysis

Genetics

Nature Biotechnology

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. Clonal dynamics are inferred from mitochondrial variants in primary human cells.

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