Single cell lineage tracing by endogenous mitochondrial DNA mutations in ATAC-seq data [stem cells and blasts]

Simultaneous measurement of lineage relationship and information on cell fate is desireable for human tissues. Here we describe a new strategy to track cell lineage using endogenous mitochondrial DNA variants in ATAC-seq data, which simultaneously measures the chromatin profiling. We first provide a proof of principle that somatic mutations in the mitochondrial genome can be used as a genetic marker to depict cellular lineage relationships and further quantified the power of lineage definition with these genetic markers. Using this method, we demonstrated the genetic and epigenetic heterogeneity of hematopoietic stem cells from patient with acute myeloid leukemia. Overall design: Single-cell ATAC-seq of leukemia stem cells and leukemic blasts from AML patients