Miller TE, Lareau CA, Verga JA, DePasquale EAK, Liu V, Ssozi D, Sandor K, Yin Y, Ludwig LS, El Farran CA, Morgan DM, Satpathy AT, Griffin GK, Lane AA, Love JC, Bernstein BE, Sankaran VG, van Galen P.
Nature Biotechnology, 24 February 2022
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.