Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics

Publication date: Available online 28 February 2019Source: CellAuthor(s): Leif S. Ludwig, Caleb A. Lareau, Jacob C. Ulirsch, Elena Christian, Christoph Muus, Lauren H. Li, Karin Pelka, Will Ge, Yaara Oren, Alison Brack, Travis Law, Christopher Rodman, Jonathan H. Chen, Genevieve M. Boland, Nir Hacohen, Orit Rozenblatt-Rosen, Martin J. Aryee, Jason D. Buenrostro, Aviv Regev, Vijay G. SankaranSummaryLineage 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.Graphical Abstract

Source: Cell - March 4, 2019 Category: Cytology Source Type: research