Helmholtz Gemeinschaft


Lineage tracing in humans enabled by mitochondrial mutations and single-cell genomics

Item Type:Article
Title:Lineage tracing in humans enabled by mitochondrial mutations and single-cell genomics
Creators Name:Ludwig, L.S. and Lareau, C.A. and Ulirsch, J.C. and Christian, E. and Muus, C. and Li, L.H. and Pelka, K. and Ge, W. and Oren, Y. and Brack, A. and Law, T. and Rodman, C. and Chen, J.H. and Boland, G.M. and Hacohen, N. and Rozenblatt-Rosen, O. and Aryee, M.J. and Buenrostro, J.D. and Regev, A. and Sankaran, V.G.
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.
Keywords:Lineage Tracing Single Cell Genomics, Somatic Mutations, Mitochondrial DNA, mtDNA, Sequencing, Hematopoiesis, Chronic Myeloid Leukemia, Colon Cancer
Publisher:Cell Press
Page Range:1325-1339
Date:7 March 2019
Official Publication:https://doi.org/10.1016/j.cell.2019.01.022
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library