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
Study at a glance
- Design
- Computational / modelling — Reanalysis of public cancer scRNA-seq and spatial datasets comparing pctMT filters, viability proxies, metabolism, and clinical correlates
- N
- N=134 · Nine public scRNA-seq datasets: 441,445 cells from 134 patients (160,225 malignant)
- Population
- Malignant and tumour-microenvironment cells across multiple human cancer types
- Outcome
- Standard >15% pctMT filters deplete viable, metabolically altered malignant HighMT cells linked to xenobiotic metabolism, drug resistance, and clinical features
Structured fields used in claim comparison tables when every cited study has a complete layer.
Inspect source passages
High-mito filters can discard living cancer cell states
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
441,445 cells from 134 patients across nine datasets
We examine nine public single-cell RNA-seq datasets from various cancers, including 441,445 cells from 134 patients, and public spatial transcriptomics data, assessing the viability of malignant cells with high pctMT.
160,225 malignant cells included
spanning the total of 441,445 cells across 134 patients, including 160,225 malignant cells (Fig. 1 ).
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
0 of 8 answers reviewed
Research intelligence for this paper
See its role on concept claims, tensions it is part of, placement history, and related discoveries.
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.
More on Gene expression