Discovering Cellular Mitochondrial Heteroplasmy Heterogeneity with Single Cell RNA and ATAC Sequencing

Area of Science:

• Genomics
• Cell Biology
• Biotechnology

Background:

• Next-generation sequencing (NGS) has transformed biological studies, particularly single-cell genomics, revealing cellular heterogeneity in transcriptional, genetic, and epigenomic states.
• Despite extensive research on cellular heterogeneity, mitochondrial heterogeneity remains underexplored in single-cell datasets.
• Single-cell sequencing offers the potential to analyze mitochondrial genomes, enabling the study of heteroplasmies at the single-cell level and their impact on cellular functions.

Purpose of the Study:

• To review the application of single-cell sequencing technologies for investigating mitochondrial heterogeneity.
• To highlight recent methods utilizing single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) for probing mitochondrial heteroplasmies.
• To discuss the potential of these modalities in understanding the interplay between mitochondrial state and cellular function.

Main Methods:

• Overview of single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) technologies.
• Summarization of current methods for analyzing mitochondrial genome coverage and heteroplasmies from single-cell data.
• Review of recent studies employing scRNA-seq and scATAC-seq to discover mitochondrial heterogeneity.

Main Results:

• Single-cell sequencing modalities like scRNA-seq and scATAC-seq provide high-throughput analysis of thousands of cells.
• These techniques enable detailed resolution of heteroplasmies alongside cellular states (transcriptional, epigenomic).
• Emerging methods are increasingly used to identify and characterize mitochondrial heterogeneity within diverse cell populations.

Conclusions:

• scRNA-seq and scATAC-seq are powerful tools for exploring mitochondrial heteroplasmy and heterogeneity at the single-cell level.
• These approaches offer new avenues to link mitochondrial variations with cellular functions and states.
• Further research is needed to address current limitations and explore future directions in single-cell mitochondrial genomics.