Single-cell lineage tracing by endogenous mutations enriched in transposase accessible mitochondrial DNA
- Stanford University, United States
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.
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Single cell lineage tracing by endogenous mitochondrial DNA mutations in ATAC-seq dataNCBI Gene Expression Omnibus, GSE122576.
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Single cell lineage tracing by endogenous mitochondrial DNA mutations in ATAC-seq dataNCBI Gene Expression Omnibus, GSE122577.
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Single-cell chromatin accessibility data using scATAC-seqNCBI Gene Expression Omnibus, GSE65360.
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ATAC-seq dataNCBI Gene Expression Omnibus, GSE74912.
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Single-cell chromatin accessibility data using scATAC-seqNCBI Gene Expression Omnibus, GSE74310.
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Single-cell epigenomics maps the continuous regulatory landscape of human hematopoietic differentiationNCBI Gene Expression Omnibus, GSE96772.
Article and author information
Author details
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.
Reviewing Editor
- Ross L Levine, Memorial Sloan Kettering Cancer Center, United States
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).
Version history
- Received: January 12, 2019
- Accepted: April 7, 2019
- Accepted Manuscript published: April 8, 2019 (version 1)
- Accepted Manuscript updated: April 9, 2019 (version 2)
- 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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Single-cell lineage tracing by endogenous mutations enriched in transposase accessible mitochondrial DNA
eLife 8:e45105.
https://doi.org/10.7554/eLife.45105
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