Quesion: Why do I see a high level of mitochondrial gene expression?
Answer: Mitochondrial genes are expressed in most cells and their expression level is cell type-specific.
High expression levels of mitochondrial genes could be an indicator of:
- Poor sample quality, leading to a high fraction of apoptotic or lysing cells.
- Biology of the particular sample, for example tumor biopsies, which may have increased mitochondrial gene expression due to metabolic activity and/or necrosis.
Apoptotic cells express mitochondrial genes and export these transcripts to the cytoplasm in mammalian cells. For example, when apoptotic cells are spiked into an otherwise healthy cell suspension, an increased number of mitochondrial genes are detected. The percentage of mitochondrial UMIs detected as a proportion of total UMIs can be seen in Figure 4 of the following Tech Note: https://support.10xgenomics.com/single-cell-gene-expression/index/doc/technical-note-removal-of-dead-cells-from-single-cell-suspensions-improves-performance-for-10x-genomics-single-cell-applications.
Lysed cells or cells with their cellular membrane disrupted release their cytoplasmic transcripts while the mitochondrial transcripts may still remain within the double-membrane bound mitochondria. Lysed cells with intact mitochondria may be partitioned into GEMs, increasing the fraction of mitochondrial transcripts detected.
If only a single or a few clusters of cells have differential upregulation of mitochondrial transcripts and a lower total UMI count, this cluster or clusters most likely represent a population of dead or dying cells.
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