Mitochondrial DNA Mutations as Natural Barcodes for Lineage Tracing of Murine Tumor Models. Academic Article uri icon

Overview

abstract

  • UNLABELLED: Murine models are indispensable tools for functional genomic studies and preclinical testing of novel therapeutic approaches. Mitochondrial single-cell assay for transposase-accessible chromatin using sequencing (mtscATAC-seq) enables the dissection of cellular heterogeneity and clonal dynamics by capturing chromatin accessibility, copy-number variations (CNV), and mitochondrial DNA (mtDNA) mutations, yet its applicability to murine studies remains unexplored. By leveraging mtscATAC-seq in novel chronic lymphocytic leukemia and Richter syndrome mouse models, we report the detection of mtDNA mutations, particularly in highly proliferative murine cells, alongside CNV and chromatin state changes indicative of clonal evolution upon secondary transplant. This study thus demonstrates the feasibility and utility of multi-modal single-cell and natural barcoding approaches to characterize murine cancer models. SIGNIFICANCE: mtDNA mutations can serve as natural barcodes to enable lineage tracing in murine cancer models, which can be used to provide new insights into disease biology and to identify therapeutic vulnerabilities.

publication date

  • March 2, 2023

Research

keywords

  • DNA, Mitochondrial
  • Neoplasms

Identity

PubMed Central ID

  • PMC9988704

Scopus Document Identifier

  • 85149183332

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-22-0275

PubMed ID

  • 36469010

Additional Document Info

volume

  • 83

issue

  • 5