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Erythropoietin receptor on cDC1s dictates immune tolerance

GSE253056 Mus musculus (mouse) RNA-seq (gene expression) 20 samples Submitted 2024/03/01 Platform GPL17021Platform GPL34328
At a glance

RNA-seq (gene expression) · mouse · 20 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)
Samples
20 samples: 8 conditions, mostly in triplicateGroups 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)
Type 1 conventional dendritic cells (cDC1s) are unique in their efferocytosis and cross-presenting abilities, resulting in T cell-mediated immunity or tolerance. However, the factors that dictate whether cDC1s induce a tolerogenic or immunogenic response remain largely unknown. Here, we show that the erythropoietin receptor (EpoR) acts as a critical switch that determines the tolerogenic function of cDC1s and the threshold of Ag-specific T cell responses.
Read the full summary ↓
In total lymphoid irradiation and anti-thymocyte serum (TLI/ATS)-induced allograft tolerance, cDC1s upregulate EpoR expression, and conditional knockout of EpoR in cDC1s diminishes antigen (Ag)-specific FOXP3+ Treg induction and expansion, resulting in allograft rejection. Mechanistically, EpoR promotes efferocytosis-induced tolerogenic maturation of splenic cDC1s towards late-stage CCR7⁺ cDC1s characterized by elevated integrin β8 gene (Itgb8) expression, and conditional knockout of Itgb8 in cDC1s impairs TLI/ATS-induced tolerance. Migratory cDC1s in peripheral lymph nodes preferentially express EpoR, and their capacity to induce FOXP3⁺ Tregs is enhanced by EPO. Reciprocally, EpoR deficiency enables immunogenic maturation of both pLN migratory and splenic CCR7⁺ cDC1s by upregulating genes essential for MHC class II-mediated Ag presentation, cross-presentation and costimulation. Loss of cDC1 EpoR reduces tumor growth by enhancing anti tumor CD8⁺ T cell immunity, particularly by promoting tumor Ag specific CD8⁺ T cell priming in tumor draining lymph nodes to generate more precursor exhausted T cells (Tpex) and by sustaining intratumoral Tpexs while decreasing Tregs. Targeting EpoR on cDC1s to either induce or inhibit immune tolerance could pave the way for novel treatments of a variety of diseases.
This dataset
Open GSE253056 in finder → Find more mouse RNA-seq datasets →
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.

Series matrix ↓
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 GSE253056_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
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.

Raw reads on ENA ↗

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 PRJNA1063723 and SRA study SRP483308. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
8 conditions, mostly in triplicate
Spleen Ctrl ×3 Spleen cKO ×3 pLN Ctrl ×3 pLN cKO ×3 cDC1s, TLI/ATS ×2 cDC1s, UNT ×2 EpoR+ cDC1s, TLI/ATS ×2 EpoR- cDC1s, TLI/ATS ×2

Supports a between-group comparison across 20 samples.

How we read this: 8 replicated groups read from 20 sample titles; they account for 20 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
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