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| Status |
Public on Apr 30, 2024 |
| Title |
CD49a expression and induction of cytotoxicity on human tissue-resident CD8+ T cells is controlled by RUNX2 and RUNX3 transcription factor activity [ATAC-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
CD49a marks highly cytotoxic epidermal tissue-resident memory (TRM)-cells, but their molecular circuitry and relationships to circulating populations are poorly defined. We demonstrate enrichment of RUNX family transcription factor binding motifs in human epidermal CD8+CD103+CD49a+ TRM-cells, paralleled by high RUNX2 and RUNX3 protein expression. Clonal overlap between epidermal CD8+CD103+CD49a+ TRM-cells and circulating memory CD8+CD45RA–CD62L+ T-cells identified a reservoir of circulating cells with potential to seed cytotoxic TRM-cells in new sites. Upon IL-15 and TGF-β stimulation, subsets of circulating CD8+CD45RA–CD62L+ T-cells acquired CD49a expression and cytotoxic transcriptional profiles in a RUNX2 and RUNX3 dependent manner. In contrast, knock-out of RUNX3, but not RUNX2, prevented CD103 expression. In melanoma, high RUNX2, but not RUNX3, transcription correlated with a cytotoxic CD8+CD103+CD49a+ TRM cell signature and overall patient survival. Together, our results indicate that combined RUNX2 and RUNX3 activity promotes the differentiation of cytotoxic CD8+CD103+CD49a+ TRM-cells, providing immunosurveillance of infected and malignant cells.
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| Overall design |
CD69+ CD8 T cells from the dermis (CD103-CD49a- and CD103+CD49a-) and epidermis (CD103+CD49a- and CD103+CD49a+) of 4 healthy donors were FACS sorted and directly used for Omni ATAC-seq.
**Submitter declares that raw data were not submitted due to patient privacy concerns**
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| Contributor(s) |
Zitti B, Pandey RV, Bryceson Y |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
May 10, 2023 |
| Last update date |
Apr 30, 2024 |
| Contact name |
Ram Vinay Pandey |
| E-mail(s) |
ramvinay.pandey@ki.se, beatrice.zitti@ki.se, yenan.bryceson@ki.se
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| Phone |
+46-(0)70-443 19 44
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| Organization name |
Karolinska Institutet
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| Department |
Department of Medicine
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| Lab |
HERM
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| Street address |
Hälsovägen 7, Neo
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| City |
Huddinge |
| State/province |
Stockholm |
| ZIP/Postal code |
141 57 |
| Country |
Sweden |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (16)
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| GSM7324281 |
Epidermis CD49a+, donor 2017#C23 |
| GSM7324282 |
Dermis CD103-, donor 2018#C37 |
| GSM7324283 |
Dermis CD103+, donor 2018#C37 |
| GSM7324284 |
Epidermis CD103+, donor 2018#C37 |
| GSM7324285 |
Epidermis CD49a+, donor 2018#C37 |
| GSM7324286 |
Dermis CD103-, donor 2018#C41 |
| GSM7324287 |
Dermis CD103+, donor 2018#C41 |
| GSM7324288 |
Epidermis CD103+, donor 2018#C41 |
| GSM7324289 |
Epidermis CD49a+, donor 2018#C41 |
| GSM7324290 |
Dermis CD103-, donor 2018#C50 |
| GSM7324291 |
Dermis CD103+, donor 2018#C50 |
| GSM7324292 |
Epidermis CD103+, donor 2018#C50 |
| GSM7324293 |
Epidermis CD49a+, donor 2018#C50 |
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| This SubSeries is part of SuperSeries: |
| GSE232239 |
CD49a expression and induction of cytotoxicity on human tissue-resident CD8+ T cells is controlled by RUNX2 and RUNX3 transcription factor activity |
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| Relations |
| BioProject |
PRJNA971337 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE232238_RAW.tar |
2.3 Gb |
(http)(custom) |
TAR (of BEDGRAPH, TXT) |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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