High-mito filters can discard living cancer cell states
Across ~441k cells from 134 patients, malignant cells often exceed 15% mitochondrial RNA without stress-death signatures and show metabolic programs relevant to therapy.
Source
Filtering cells with high mitochondrial content depletes viable metabolically altered malignant cell populations in cancer single-cell studies
What they did
Yates et al. reanalyzed nine public cancer scRNA-seq datasets (441,445 cells; 134 patients) plus spatial data, comparing pctMT in malignant vs TME compartments, dissociation-stress scores, metabolic pathways, cell-line drug resistance, and clinical associations using a 15% HighMT cutoff.
What they found
Malignant cells have higher pctMT without higher dissociation-stress scores. HighMT malignant cells show metabolic dysregulation including xenobiotic metabolism and drug-resistance links. In many tumors, 10–50% of samples have ≥2× HighMT fraction in malignant vs TME compartments—so standard filters remove real biology.
The limits
What it doesn't show
pctMT is not a perfect viability assay; thresholds may still need experiment-specific tuning. Observational public data cannot prove HighMT cells cause resistance in patients.
Key terms
- pctMT
- Percentage of RNA counts from mitochondrial genes in a cell.
- HighMT
- Cells with pctMT above a threshold (here typically >15%).
- Quality-control filtering
- Removing putative low-quality/dying cells before downstream scRNA-seq analysis.
- TME
- Tumor microenvironment nonmalignant cells compared with malignant compartment.
- Xenobiotic metabolism
- Pathways handling drugs/toxins enriched in HighMT malignant cells.
- Dissociation-induced stress
- Artifact gene programs from tissue dissociation; not elevated with HighMT here.
Flashcards
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Quiz yourself
Approx. cells reanalyzed?
Common questions
Why do people filter high pctMT cells?
High mitochondrial RNA is often treated as a death/low-quality marker.
Are HighMT malignant cells just dying?
Not necessarily—they lack elevated dissociation-stress scores and show coherent metabolic states.
What cutoff defines HighMT here?
pctMT >15%, within the common 10–20% literature range.
Scale of the reanalysis?
441,445 cells from 134 patients across nine cancer datasets.
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