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Mitochondrial DNA mutations as natural barcodes for lineage tracing of murine tumor models

Item Type:Article
Title:Mitochondrial DNA mutations as natural barcodes for lineage tracing of murine tumor models
Creators Name:Penter, L. and Ten Hacken, E. and Southard, J. and Lareau, C. and Ludwig, L.S. and Li, S. and Neuberg, D.S. and Livak, K.J. and Wu, C.J.
Abstract:Murine models are indispensable tools for functional genomic studies and preclinical testing of novel therapeutic approaches. Mitochondrial single-cell assay for transposase-accessible chromatin (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.
Keywords:Chronic Lymphocytic Leukemia, Single Cell Sequencing, Chromatin Accessibility, Mitochondrial, DNA Mutations, Lineage Tracing, Animals, Mice
Source:Cancer Research
ISSN:0008-5472
Publisher:American Association for Cancer Research
Date:5 December 2022
Official Publication:https://doi.org/10.1158/0008-5472.can-22-0275
PubMed:View item in PubMed

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