Omics · study · 2026
Metabolically and epigenetically reprogrammed splenic TRNP1hiCD8+ T cells exacerbate liver fibrosis
Listed in NCBI GEO
MASLD, especially its severe form MASH, progresses to liver fibrosis, leading to cirrhosis and liver cancer.
Description
The crosstalk between spleen and liver in MASLD/MASH progression remains poorly understood. Here, we find the enlarged spleens in MASLD patients, and the induced TRNP1hiCD8+ T cells in the spleens of MASLD/MASH mouse models and confirmed in MASLD patients, with pro-fibrotic property by secreting INSR-α.
Mechanistically, demethylated DNA and H3K27me3, increased H3K27ac, together with bolstered enhancer-promoter contact, synergistically reorganized chromatin topologically associating domains spatially to initiate the expression of transcription factor TRNP1 in splenic CD8+ T cells. TRNP1 then transcriptionally activates the expression of FURIN and CTSD, promoting the maturation and ectodomain shedding of INSR-α thereby facilitating its secretion to activate hepatic stellate cells.
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In vivo blockade of INSR-α using neutralizing antibodies alleviates MASLD/MASH-induced liver fibrosis. Therefore, this study reveals splenic TRNP1hiCD8+ T cells with pro-fibrotic property and suggests a potential anti-fibrotic strategy.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE295nnn/GSE295165 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE295165 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1253651 ncbi.nlm.nih.gov/bioproject/PRJNA1253651 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Related
- Possibly the same asMetabolically and epigenetically reprogrammed splenic TRNP1hiCD8+ T cells exacerbate liver fibrosis
- Possibly the same asMetabolically and epigenetically reprogrammed splenic TRNP1hiCD8+ T cells exacerbate liver fibrosis
- Possibly the same asMetabolically and epigenetically reprogrammed splenic TRNP1hiCD8+ T cells exacerbate liver fibrosis
- Possibly the same asMetabolically and epigenetically reprogrammed splenic TRNP1hiCD8+ T cells exacerbate liver fibrosis
- Possibly the same asMetabolically and epigenetically reprogrammed splenic TRNP1hiCD8+ T cells exacerbate liver fibrosis
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE295165 | 10 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[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 |