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Mitochondrial genetics through the lens of single-cell multi-omics

Item Type:Review
Title:Mitochondrial genetics through the lens of single-cell multi-omics
Creators Name:Nitsch, L., Lareau, C.A. and Ludwig, L.S.
Abstract:Mitochondria carry their own genetic information encoding for a subset of protein-coding genes and translational machinery essential for cellular respiration and metabolism. Despite its small size, the mitochondrial genome, its natural genetic variation and molecular phenotypes have been challenging to study using bulk sequencing approaches, due to its variation in cellular copy number, non-Mendelian modes of inheritance and propensity for mutations. Here we highlight emerging strategies designed to capture mitochondrial genetic variation across individual cells for lineage tracing and studying mitochondrial genetics in primary human cells and clinical specimens. We review recent advances surrounding single-cell mitochondrial genome sequencing and its integration with functional genomic readouts, including leveraging somatic mitochondrial DNA mutations as clonal markers that can resolve cellular population dynamics in complex human tissues. Finally, we discuss how single-cell whole mitochondrial genome sequencing approaches can be utilized to investigate mitochondrial genetics and its contribution to cellular heterogeneity and disease.
Keywords:Mitochondrial DNA, Genetic Variation, Mitochondrial Genome, Genomics, Mitochondria, Multiomics, Mutation, Single-Cell Analysis
Source:Nature Genetics
ISSN:1061-4036
Publisher:Nature Publishing Group
Volume:56
Number:7
Page Range:1355-1365
Date:July 2024
Official Publication:https://doi.org/10.1038/s41588-024-01794-8
PubMed:View item in PubMed

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