|
| Status |
Public on Jan 01, 2024 |
| Title |
Donor regulatory T cells rapidly adapt to recipient tissues to control acute graft-versus-host disease [scRNA-seq & scTCR-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
|
| Summary |
Adoptive transfer of donor regulatory T cells (Treg) is a promising treatment option for Graft-versus-Host disease (GvHD), but has not yet found its way into routine clinical practice. To map distinctive properties of protective Treg (generated by either polyclonal or allogeneic in vitro expansion), we followed their fate in recipient organs (spleen, liver, colon) in a prophylactic mouse model of MHC-mismatched bone-marrow transplantation (BMT). Using comprehensive gene expression and T cell receptor profiling, we show that both in vitro expansion protocols generated Treg products that preserved hallmark Treg properties, ameliorated GvHD symptoms, retained their phenotypic plasticity and rapidly acquired organ-specific gene expression profiles after BMT, comparable to their tissue-resident counterparts. When co-transplanted with GvHD-inducing T cells, Treg enabled hallmark suppressive and cytotoxic features, most evidently in the colon. Dominant Treg T cell receptor clonotypes were evenly distributed between organs and across recipients, suggesting a major role of ubiquitous alloantigen-specific Treg in controlling GvHD. Effective protection inversely correlated with the relative abundance of organ-specific Treg, that were transcriptionally distinct, less “activated” and preferentially accumulated in the colon of recipients receiving polyclonally expanded Treg. In summary, we provide a detailed atlas of Treg selection and adaptation in the prophylactic therapy of GvHD.
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| |
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| Overall design |
Donor Treg were reisolated from recipient mice in a GvHD model and sequenced (singleCell RNASeq, TCRSeq)
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| |
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| Contributor(s) |
Dittmar D, Pielmeier F, Stanewsky H, Rehli M, Strieder N |
| Citation missing |
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| |
| Submission date |
Jan 26, 2023 |
| Last update date |
Jan 01, 2024 |
| Contact name |
Michael Rehli |
| E-mail(s) |
michael.rehli@klinik.uni-r.de
|
| Organization name |
University Hospital Regensburg
|
| Department |
Internal Med III
|
| Street address |
F.-J.-Strauss-Allee 11
|
| City |
Regensburg |
| ZIP/Postal code |
93042 |
| Country |
Germany |
| |
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| Platforms (2) |
| GPL21626 |
NextSeq 550 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (21)
|
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| This SubSeries is part of SuperSeries: |
| GSE223800 |
Donor regulatory T cells rapidly adapt to recipient tissues to control acute graft-versus-host disease |
|
| Relations |
| BioProject |
PRJNA928408 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE223798_Counts_Colon_filtered.tsv.gz |
24.4 Mb |
(ftp)(http) |
TSV |
| GSE223798_Counts_Colon_filtered_annotation.tsv.gz |
128.8 Kb |
(ftp)(http) |
TSV |
| GSE223798_Counts_Colon_filtered_metainfo_TCRchain_TRA.tsv.gz |
1.0 Mb |
(ftp)(http) |
TSV |
| GSE223798_Counts_Colon_filtered_metainfo_TCRchain_TRB.tsv.gz |
1.0 Mb |
(ftp)(http) |
TSV |
| GSE223798_Counts_filtered.tsv.gz |
63.1 Mb |
(ftp)(http) |
TSV |
| GSE223798_Counts_filtered_annotation.tsv.gz |
321.1 Kb |
(ftp)(http) |
TSV |
| GSE223798_Counts_filtered_metainfo_TCRchain_TRA.tsv.gz |
2.5 Mb |
(ftp)(http) |
TSV |
| GSE223798_Counts_filtered_metainfo_TCRchain_TRB.tsv.gz |
2.5 Mb |
(ftp)(http) |
TSV |
| GSE223798_RAW.tar |
476.6 Mb |
(http)(custom) |
TAR (of LOOM, TAR) |
| GSE223798_Seurat_Sel_anndata_02062022.h5ad.gz |
2.4 Mb |
(ftp)(http) |
H5AD |
| GSE223798_Seurat_SingleCellRNA_plusTCR.rds.gz |
4.5 Gb |
(ftp)(http) |
RDS |
| GSE223798_SingleCellRNA_full_zk.h5ad.gz |
4.8 Gb |
(ftp)(http) |
H5AD |
| GSE223798_anndata_colon_p36_scvelo.h5ad.gz |
11.5 Mb |
(ftp)(http) |
H5AD |
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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