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.
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.
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
- Ross L Levine, Memorial Sloan Kettering Cancer Center, United States
Publication 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.
Metrics
-
- 7,226
- Page views
-
- 1,014
- Downloads
-
- 28
- Citations
Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.