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

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2019 Mar 5

PMID 30827679

Citations 234

Authors

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 Sankaran

Affiliations

Soon will be listed here.

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.

Citing Articles

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