Single-cell multi-omic analysis of mitochondrial mutational mosaicism and dynamics - PubMed
6 hours ago
- #mutational mosaicism
- #mitochondrial DNA
- #single-cell analysis
- Single-cell multi-omic analysis reveals mitochondrial DNA (mtDNA) mutational mosaicism and dynamics.
- Introduction of two metrics: scmtMPM (single-cell mtDNA mutations per million base pairs) and scwMSS (heteroplasmy-weighted mitochondrial local constraint scores).
- Study uses POLGD274A knock-in HEK293 cell lines to analyze mutational loads and somatic mosaicism.
- Findings show complex mutational landscapes in individual cells with pathogenic mutations at subthreshold levels, indicating negative selection.
- Identifies constrained mutations in complex I in both healthy donors and mitochondriopathy patients.
- Highlights previously unrecognized heterogeneity in mtDNA mutational landscapes at the single-cell level.
- Provides a framework for investigating mitochondrial genetics, disease, and somatic mosaicism.
- Broad Institute has filed patents related to the technologies described, with some authors named as inventors.