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| Status |
Public on Jul 05, 2023 |
| Title |
10X single-cell RNA-seq profiling of T cells from the pancreas, pancreatic lymph nodes, and blood of NOD mice with spontaneous or anti-PD-1-induced Type 1 Diabetes |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Immune-related adverse events (irAEs) are a notable complication of PD-1 cancer immunotherapy. A better understanding of how these iatrogenic diseases compare to naturally arising autoimmune diseases is needed for treatment and monitoring of irAEs. We identified differences in anti-PD-1-induced Type 1 Diabetes (T1D) and spontaneous T1D in non-obese diabetic (NOD) mice by performing single-cell RNA-seq and TCR-seq on T cells from the pancreas, pancreas-draining lymph node (pLN), and blood of mice with PD-1-induced T1D or spontaneous T1D. In the pancreas, anti-PD-1 resulted in expansion of terminally-exhausted/effector-like CD8+ T cells, an increase in T-bethi CD4+FoxP3- T cells, and a decrease in memory CD4+FoxP3- and CD8+ T cells in contrast to spontaneous T1D. Notably, anti-PD-1 caused increased TCR sharing between the pancreas and the periphery. Moreover, T cells in the blood of anti-PD-1-treated mice expressed markers that differed from spontaneous T1D, suggesting that the blood may provide a window to monitor irAEs rather than relying exclusively on the autoimmune target organ.
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| Overall design |
10X 5' single cell RNASeq and paired TCR sequencing was performed on sorted TCR-beta+CD11A+ T cells from the pancreas, pancreatic lymph nodes, and peripheral blood of NOD mice. Samples from individual mice were labeled using hashtag antibodies and detected using CITE-seq. Using the TCR sequence as a molecular barcode, we identified matching T cell clones between the pancreatic lymph node, blood and pancreas, and characterized the matching versus non-matching T cell populations within a tissue compartment and between tissue compartments.
Please note that processed data files generated from both *FB* and *GEX* raw data are linked to the corresponding *GEX* sample records.
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| Web link |
http://10.1084/jem.20221920
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| Contributor(s) |
Collier JL, Pauken KE, Sharpe AH |
| Citation(s) |
37432393 |
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| Submission date |
Mar 26, 2023 |
| Last update date |
Jul 28, 2023 |
| Contact name |
Jenna Lynn Collier |
| Organization name |
Harvard University
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| Department |
Immunology
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| Street address |
77 Avenue Louis Pasteur
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| City |
Boston |
| State/province |
Massachusetts |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (27)
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| Relations |
| BioProject |
PRJNA948872 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE228233_RAW.tar |
337.6 Mb |
(http)(custom) |
TAR (of CSV, MTX, TSV) |
| GSE228233_all_cells_integrated.rds.gz |
1.0 Gb |
(ftp)(http) |
RDS |
| GSE228233_cd4_pancreas_only.rds.gz |
249.9 Mb |
(ftp)(http) |
RDS |
| GSE228233_cd8_pancreas_only.rds.gz |
197.9 Mb |
(ftp)(http) |
RDS |
| GSE228233_feature_barcoding_antibody_reference.csv.gz |
250 b |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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