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

Elife. 2019 Apr 9:8:e45105. doi: 10.7554/eLife.45105.


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.

Keywords: ATAC-seq; EMBLEM; acute myeloid leukemia; cancer biology; genetics; genomics; hematopoietic stem cells; human; lineage tracing; mitochondrial DNA mutations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Lineage*
  • Clonal Evolution
  • Cytological Techniques / methods*
  • DNA, Mitochondrial / genetics*
  • Hematopoietic Stem Cells / pathology*
  • Humans
  • Leukemia, Myeloid, Acute / pathology*
  • Mutation*
  • Sensitivity and Specificity


  • DNA, Mitochondrial

Associated data

  • GEO/GSE122576
  • GEO/GSE122577
  • GEO/GSE47753
  • GEO/GSE65360
  • GEO/GSE74912
  • GEO/GSE74310
  • GEO/GSE96772