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Tissue-specific reprogramming leads to angiogenic neutrophil specialization and tumor vascularization in colorectal cancer

GSE232217 Mus musculus (mouse) RNA-seq (gene expression) 28 samples Submitted 2024/04/01 Platform GPL21103Platform GPL20301
At a glance

RNA-seq (gene expression) · mouse · 28 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Topic
Colorectal cancerThis series is part of our curated briefing on it.
Samples
28 samples: 10 conditions, mostly in duplicateGroups 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.
Paper
Tissue-specific reprogramming leads to angiogenic neutrophil specialization and tumor vascularization in colorectal cancerThe Journal of clinical investigation · 2024
Summary (written by the submitters)
Polymorphonuclear neutrophil (PMN) tissue accumulation is an established feature of ulcerative colitis (UC) lesions and colorectal cancer (CRC). Given the emerging evidence of PMN phenotypic and functional heterogeneity, we analyzed the transcriptomic landscape of PMNs in blood and tissue during the spatiotemporal transition from inflammatory ulceration to CRC.
Read the full summary ↓
Based on their transcriptional programs, PMNs were effectively stratified into distinct spatial compartments of peripheral blood, inflamed colon tissue, and the tumor niche. In silico pathway overrepresentation analysis, protein-network mapping, gene signature identification, and gene-ontology scoring revealed unique enrichment of angiogenic and vasculature development pathways in tumor-associated neutrophils (TANs). Functional studies utilizing ex vivo cultures, colitis-induced murine CRC, and patient-derived xenograft models demonstrated a critical role for TANs in promoting tumor vascularization. Spp1 (OPN) and Mmp14 (MT1-MMP) were identified by unbiased -omics and by mechanistic studies to be highly induced in TANs and function to critically regulate endothelial cell chemotaxis and branched network formation. TCGA dataset and clinical specimens confirmed enrichment of SPP1 and MMP14 in high-grade CRC but not in UC patients. Importantly, pharmacological inhibition of TAN trafficking or MMP14 activity effectively reduced tumor vascular density, leading to CRC regression. The current study identified a niche-directed PMN transcriptional reprograming and functional specialization, highlighting emerging PMN plasticity. Our findings define new TAN contributions to tumor vascularization, delineating a new therapeutic framework for CRC treatment focused on TAN angiogenic properties.
Published in
Tissue-specific reprogramming leads to angiogenic neutrophil specialization and tumor vascularization in colorectal cancer
Bui TM, Yalom LK, Ning E et al. · The Journal of clinical investigation 2024 · PMID 38329810 · doi:10.1172/JCI174545
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 GSE232217_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA971230 and SRA study SRP436917. Searching any of these in the dataset finder brings you back here.

Study design
10 conditions, mostly in duplicate
PDX MMP14i-treated ×5 PDX anti-OPN-treated ×5 PDX vehicle-treated ×4 Healthy blood neutrophils/PMNs ×2 DSS colitis blood neutrophils/PMNs ×2 DSS colitis colonic neutrophils/PMNs ×2 AOM/DSS early tumor (w8) blood neutrophils/PM… ×2 AOM/DSS advanced tumor (w13) blood neutrophil… ×2 +2 more

Supports a case/control comparison: 18 samples read as cases, 2 as controls.

How we read this: 10 replicated groups read from 28 sample titles; they account for 28 of them. 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
More Colorectal cancer datasets

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