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Blocking the transfer of damaged mitochondria from cancer cells to RGS5+ MYL9+ CAFs reduces persistent tolerance to TKIs in EGFR-mutant lung cancer

GSE294147 Homo sapiens (human) Single-cell RNA-seq 18 samples Submitted 2025/11/20 Platform GPL24676
At a glance

Single-cell RNA-seq · human · 18 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Homo sapiens (human)
Topic
Lung cancerThis series is part of our curated briefing on it.
Samples
18 samples: 18 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
Eliminating drug-tolerant persister (DTP) cells remain a significant challenge in overcoming resistance to tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung adenocarcinoma. Utilizing single-cell RNA sequencing, we identify a novel RGS5+MYL9+ cancer associated fibroblasts (CAFs) subset. This subset is linked to TKI resistance and correlates with poorer prognosis.
Read the full summary ↓
The RGS5+MYL9+ CAFs are spatially positioned close to DTP cells, a proximity facilitated by CCL11 recruitment from DTP cells. TKIs induced mitochondria ROS activates Rho GTPase 1 (Miro1) and RhoA of tumor cells, subsequently promoting the formation of tunneling nanotube connections with neighboring RGS5+MYL9+ CAFs. These CAFs play a protective role for DTP cells, aiding in the transfer of damaged mitochondria from tumor cells through these nanotubes. By employing the Rho kinase inhibitor Fasudil to block this transfer of damaged mitochondria, we observed a significant reduction in persistent tolerance to Osimertinib in a xenograft mouse model. Our study highlights the critical role of RGS5+MYL9+ CAFs in mediating resistance to EGFR-TKIs and suggests potential therapeutic strategies for overcoming this challenge.
This dataset
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE294147_RAW.tar (it can run to tens of gigabytes).

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1248462 and SRA study SRP577478. Searching any of these in the dataset finder brings you back here.

Study design
18 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 18 sample titles: 18 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.