Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics
Name
nihms-1518665.pdf
Description
Accepted version
Size
1.53 MB
Format
Adobe PDF
Checksum (MD5)
67092a37fb93de3c78478cfee7940363
Author(s)
Regev, Aviv
Date Issued
March 2019
Journal
Cell
Publisher
Elsevier BV
Citation
Ludwig, Leif S. et al. “Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics.” Cell 176 (2019): 1325-1339.e22 © 2019 The Author(s)
Version
Author's final manuscript
Abstract
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. Using single-cell sequencing technologies, somatic mutations in mtDNA can be used as natural genetic barcodes to study cellular states and clonal dynamics.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.CELL.2019.01.022
