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Single-cell lineage tracing by endogenous mutations enriched in transposase accessible mitochondrial DNA

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Cite this article as: eLife 2019;8:e45105 doi: 10.7554/eLife.45105

Abstract

Simultaneous measurement of cell lineage and cell fates is a longstanding goal in biomedicine. Here we describe EMBLEM, a strategy to track cell lineage using endogenous mitochondrial DNA variants in ATAC-seq data. We show that somatic mutations in mitochondrial DNA can reconstruct cell lineage relationships at single cell resolution with high sensitivity and specificity. Using EMBLEM, we define the genetic and epigenomic clonal evolution of hematopoietic stem cells and their progenies in patients with acute myeloid leukemia. EMBLEM extends lineage tracing to any eukaryotic organism without genetic engineering.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE122576 and GSE122577.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Jin Xu

    Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0944-9835
  2. Kevin Nuno

    Department of Medicine, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  3. Ulrike M Litzenburger

    Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  4. Yanyan Qi

    Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  5. M Ryan Corces

    Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  6. Ravindra Majeti

    Department of Medicine, Stanford University, Stanford, United States
    For correspondence
    rmajeti@stanford.edu
    Competing interests
    Ravindra Majeti, Reviewing editor, eLife.
  7. Howard Y Chang

    Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States
    For correspondence
    howchang@stanford.edu
    Competing interests
    Howard Y Chang, is a co-founder of Accent Therapeutics and an advisor for 10x Genomics and Spring Discovery. Stanford University has filed a patent on ATAC-seq(US20160060691A1), on which HYC is named as an inventor..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9459-4393

Funding

National Human Genome Research Institute (P50-HG007735)

  • Howard Y Chang

Howard Hughes Medical Institute

  • Howard Y Chang

National Cancer Institute (R01HL142637)

  • Ravindra Majeti

National Cancer Institute (R01CA188055)

  • Ravindra Majeti

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: AML samples were obtained from patients at the Stanford Medical Center with informed consent, according to institutional review board (IRB)-approved protocols (Stanford IRB, 18329 and 6453).

Reviewing Editor

  1. Ross L Levine, Memorial Sloan Kettering Cancer Center, United States

Publication history

  1. Received: January 12, 2019
  2. Accepted: April 7, 2019
  3. Accepted Manuscript published: April 8, 2019 (version 1)
  4. Accepted Manuscript updated: April 9, 2019 (version 2)
  5. Version of Record published: April 17, 2019 (version 3)

Copyright

© 2019, Xu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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