Center for Personal Dynamic Regulomes, Stanford, United States; Department of Dermatology, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United States
Kevin Nuno
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, United States; Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, United States
Ulrike M Litzenburger
Center for Personal Dynamic Regulomes, Stanford, United States; Department of Dermatology, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United States
Yanyan Qi
Center for Personal Dynamic Regulomes, Stanford, United States; Department of Dermatology, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United States
M Ryan Corces
Center for Personal Dynamic Regulomes, Stanford, United States; Department of Dermatology, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United States
Ravindra Majeti
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, United States; Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, United States
Center for Personal Dynamic Regulomes, Stanford, United States; Department of Dermatology, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United States; Howard Hughes Medical Institute, Stanford University, Stanford, United States
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.
