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

Nat Biotechnol. 2022 Jul;40(7):1030-1034. doi: 10.1038/s41587-022-01210-8. Epub 2022 Feb 24.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA, Mitochondrial* / genetics
  • High-Throughput Nucleotide Sequencing* / methods
  • Humans
  • Mitochondria / genetics
  • Mutation
  • Sequence Analysis, RNA
  • Single-Cell Analysis

Substances

  • DNA, Mitochondrial