Omics · study · 2026
Smad4 and Eomes converge on a shared transcriptional program associated with inflammatory CD8 T-cell differentiation
Listed in NCBI GEO
The ability of CD8 T cells to mediate protective immunity while limiting immunopathology depends on critical transcription factors such as Smad4 and Eomes that regulate differentiation of activated CTLs.
Description
Disruption of transcriptional programs mediated by Eomes (30-32) and Smad4 (26, 33, 34) in activated CTLs has been implicated in viral infections, chronic inflammation and cancer. Smad4 and Eomes have been shown to be critical for differentiation of memory cells, particularly TRM cells.
To understand the gene regulation programs mediated by Smad4 and Eomes, we have done an integrated RNAseq and ChIPseq analysis using CD8 T cells that are isolated from Smad4KO (S4KO), EomesKO, and Smad3/Smad4-DKO (S34-DKO) mice. We identified overlapping and distinct gene expression programs associated with Smad4 and Eomes that shape activated CD8 T cell identity and functional bias. They act as critical regulators of genes involved in T cell differentiation, metabolic programming and epigenetic control in CD8 T cells.
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Smad4 and Eomes regulate the genes involved in tissue residency and OXPHOS-linked mitochondrial bioenergetics. Finally, we showed that canonical TGF signaling is active in the absence of Smad4 or Eomes and abrogated only when both Smad3 and Smad4 are deleted. Surprisingly, CD8 T cells lacking both Smad3 and Smad4 are more enriched for TRM signature genes compared to Smad4 or Eomes-deficient CD8 T cells.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE338nnn/GSE338265 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE338265 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1493078 ncbi.nlm.nih.gov/bioproject/PRJNA1493078 ↗
project · from NCBI GEO
- PubMed 42676718 pubmed.ncbi.nlm.nih.gov/42676718 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75% · RNA sequencing 65%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE338265 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |