Journal
CELL
Volume 176, Issue 6, Pages 1325-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2019.01.022
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Funding
- NIH [F31 CA232670, 5T32 GM007226-43, 5T32CA207021-03, R33 CA202820, R01 DK103794, R33 HL120791, R01 CA208756]
- Broad Institute Fellows program
- Allen Institute Distinguished Investigator Award
- German Research Foundation (DFG)
- Broad Institute SPARC grant
- New York Stem Cell Foundation (NYSCF)
- Howard Hughes Medical Institute
- Klarman Cell Observatory
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Lineage tracing provides key insights into the fate of individual cells in complex organisms. Although effective genetic labeling approaches are available in model systems, in humans, most approaches require detection of nuclear somatic mutations, which have high error rates, limited scale, and do not capture cell state information. Here, we show that somatic mutations in mtDNA can be tracked by single-cell RNA or assay for transposase accessible chromatin (ATAC) sequencing. We leverage somatic mtDNA mutations as natural genetic barcodes and demonstrate their utility as highly accurate clonal markers to infer cellular relationships. We track native human cells both in vitro and in vivo and relate clonal dynamics to gene expression and chromatin accessibility. Our approach should allow clonal tracking at a 1,000-fold greater scale than with nuclear genome sequencing, with simultaneous information on cell state, opening the way to chart cellular dynamics in human health and disease.
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