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

Abstract
Data availability
Article and author information
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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

1. Xu J
2. Chang HY
(2018) Single cell lineage tracing by endogenous mitochondrial DNA mutations in ATAC-seq data
NCBI Gene Expression Omnibus, GSE122576.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE122576
1. Xu J
2. Chang HY
(2018) Single cell lineage tracing by endogenous mitochondrial DNA mutations in ATAC-seq data
NCBI Gene Expression Omnibus, GSE122577.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE122577

The following previously published data sets were used

(2013) Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position
NCBI Gene Expression Omnibus, GSE47753.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE47753
1. Buenrostro JD
(2015) Single-cell chromatin accessibility data using scATAC-seq
NCBI Gene Expression Omnibus, GSE65360.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65360
1. Buenrostro JD
(2016) ATAC-seq data
NCBI Gene Expression Omnibus, GSE74912.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE74912
1. Buenrostro JD
(2016) Single-cell chromatin accessibility data using scATAC-seq
NCBI Gene Expression Omnibus, GSE74310.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE74310
1. Buenrostro JD
(2018) Single-cell epigenomics maps the continuous regulatory landscape of human hematopoietic differentiation
NCBI Gene Expression Omnibus, GSE96772.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE96772

Article and author information

Author details

Jin Xu

Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0003-0944-9835
Kevin Nuno

Department of Medicine, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
Ulrike M Litzenburger

Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
Yanyan Qi

Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
M Ryan Corces

Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States

For correspondence
rcorces@stanford.edu

Competing interests
No competing interests declared.
Ravindra Majeti

Department of Medicine, Stanford University, Stanford, United States

For correspondence
rmajeti@stanford.edu

Competing interests
Ravindra Majeti, Reviewing editor, eLife.
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..

"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).

Copyright

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.