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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 [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Third-party reanalysis
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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 |
Bulk RNA-seq upon in vitro differentiation. Memory CD45RA- CD62L+ CD27+ CD8 T cells have been FACS sorted from 3 healthy donors and used for bulk RNA-seq (day 1) or differentiated in vitro for 14 days in Trm-like polarizing conditions including IL-15, TGF-b and CD3/28 stimulation in ECM-coated wells. Upon differentiation, CD8 T cells have been FACS sorted on the basis of CD69, CD103 and CD49a expression for bulk RNA-seq.
Bulk RNA-seq upon RUNT transcription factors gene deletion. CRISPR/Cas9 gene deletion was performed for RUNX2, RUNX3 and a control gene on FACS sorted memory CD45RA- CD62L+ CD27+ CD8 T cells from 5 healthy donors. Subsequently, edited cells have been cultured in in vitro for 14 days in Trm-like polarizing conditions including IL-15, TGF-b and CD3/28 stimulation in ECM-coated wells. Upon differentiation, bulk CD8 T cells have been FACS sorted for bulk RNA-seq. Two different targeting guides were used for both RUNX2 (AB and AC) and RUNX3 (AD and AE).
Bulk RNA-seq on skin Trm cells. CD103+ CD49a- and CD103+ CD49a+ CD8 Trm cells from the skin epidermis of 6 healthy donors were FACS sorted in RNA lyses buffer and used for bulk RNAseq.
This dataset includes a re-analysis of 12 Samples in GSE83637 (GSM2211621-GSM2211624, GSM2211627-GSM2211634). The processed data for this re-analysis is included in the supplementary file GSE232236_GSE83637_RNAseq_raw_gene_count_matrix.txt. This file include raw read counts for each re-analysis Sample.
**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 (39)
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| GSM7324230 |
CD103+ CD49a+ Day 14 replicate 1 |
| GSM7324231 |
CD103-cCD49a+ Day 14 replicate 1 |
| GSM7324232 |
CM Day 1 replicate 2 |
| GSM7324233 |
CD103- CD49a- Day 14 replicate 2 |
| GSM7324234 |
CD103+ CD49a- Day 14 replicate 2 |
| GSM7324235 |
CD103+ CDD49a+ Day 14 replicate 2 |
| GSM7324236 |
CD103- CD49a+ Day 14 replicate 2 |
| GSM7324237 |
CM Day 1 replicate 3 |
| GSM7324238 |
CD103- CD49a- Day 14 replicate 3 |
| GSM7324239 |
CD103+ CD49a- Day 14 replicate 3 |
| GSM7324240 |
CD103+ CD49a+ Day 14 replicate 3 |
| GSM7324241 |
CD103- CD49a+ Day 14 replicate 3 |
| GSM7324242 |
CD8 T cells, Ctrl, Donor 1_E93 |
| GSM7324243 |
CD8 T cells, Ctrl, Donor 2_E93 |
| GSM7324244 |
CD8 T cells, Ctrl, Donor 3_E95 |
| GSM7324245 |
CD8 T cells, Ctrl, Donor 4_E95 |
| GSM7324246 |
CD8 T cells, Ctrl, Donor 5_E95 |
| GSM7324247 |
CD8 T cells, Runx2_AB, Donor 1_E93 |
| GSM7324248 |
CD8 T cells, Runx2_AB, Donor 2_E93 |
| GSM7324249 |
CD8 T cells, Runx2_AB, Donor 3_E95 |
| GSM7324250 |
CD8 T cells, Runx2_AB, Donor 4_E95 |
| GSM7324251 |
CD8 T cells, Runx2_AB, Donor 5_E95 |
| GSM7324252 |
CD8 T cells, Runx2_AC, Donor 1_E93 |
| GSM7324253 |
CD8 T cells, Runx2_AC, Donor 2_E93 |
| GSM7324254 |
CD8 T cells, Runx2_AC, Donor 3_E95 |
| GSM7324255 |
CD8 T cells, Runx2_AC, Donor 4_E95 |
| GSM7324256 |
CD8 T cells, Runx2_AC, Donor 5_E95 |
| GSM7324257 |
CD8 T cells, Runx3_AD, Donor 1_E93 |
| GSM7324258 |
CD8 T cells, Runx3_AD, Donor 2_E93 |
| GSM7324259 |
CD8 T cells, Runx3_AD, Donor 3_E95 |
| GSM7324260 |
CD8 T cells, Runx3_AD, Donor 4_E95 |
| GSM7324261 |
CD8 T cells, Runx3_AD, Donor 5_E95 |
| GSM7324262 |
CD8 T cells, Runx3_AE, Donor 1_E93 |
| GSM7324263 |
CD8 T cells, Runx3_AE, Donor 2_E93 |
| GSM7324264 |
CD8 T cells, Runx3_AE, Donor 4_E95 |
| GSM7324265 |
CD8 T cells, Runx3_AE, Donor 5_E95 |
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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 |
| Reanalysis of |
GSM2211621 |
| Reanalysis of |
GSM2211622 |
| Reanalysis of |
GSM2211623 |
| Reanalysis of |
GSM2211624 |
| Reanalysis of |
GSM2211627 |
| Reanalysis of |
GSM2211628 |
| Reanalysis of |
GSM2211629 |
| Reanalysis of |
GSM2211630 |
| Reanalysis of |
GSM2211631 |
| Reanalysis of |
GSM2211632 |
| Reanalysis of |
GSM2211633 |
| Reanalysis of |
GSM2211634 |
| BioProject |
PRJNA971331 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE232236_GSE83637_RNAseq_raw_gene_count_matrix.txt.gz |
34.0 Kb |
(ftp)(http) |
TXT |
| GSE232236_RNAseq_KO_raw_gene_count_matrix.txt.gz |
2.4 Mb |
(ftp)(http) |
TXT |
| GSE232236_RNAseq_in_vitro_raw_gene_count_matrix.txt.gz |
2.0 Mb |
(ftp)(http) |
TXT |
| Processed data are available on Series record |
| Raw data not provided for this record |
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