摘要：SummaryCells transmit their genomes vertically to daughter cells during cell divisions. Here, we demonstrate the occurrence and extent of horizontal mitochondrial (mt)DNA acquisition between cells that are not in a parent-offspring relationship. Extensive single-cell sequencing from various tissues and organs of adult chimeric mice composed of cells carrying distinct mtDNA haplotypes showed that a substantial fraction of individual cardiomyocytes, neurons, glia, intestinal, and spleen cells captured donor mtDNA at high levels. In addition, chimeras composed of cells with wild-type and mutant mtDNA exhibited increased trafficking of wild-type mtDNA to mutant cells, suggesting that horizontal mtDNA transfer may be a compensatory mechanism to restore compromised mitochondrial function. These findings establish the groundwork for further investigations to identify mtDNA donor cells and mechanisms of transfer that could be critical to the development of novel gene therapies.Graphical abstractDisplay OmittedHighlights•Individual cells in adult mouse chimeras acquire donor mtDNA horizontally•Significant percentage of cardiomyocytes, neurons, and glia were heteroplasmic•Donor mtDNA heteroplasmy in these cells can reach up to 50%•Pathogenic mtDNA mutations may potentiate horizontal acquisition of wild-type mtDNAMolecular biology; Cell biology; Developmental biology
