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| Status |
Public on Nov 05, 2023 |
| Title |
Multimodal profiling reveals site-specific adaptation and tissue residency hallmarks of γδ T cells across organs in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
γδ T cells perform heterogeneous functions in homeostasis and disease across tissues. However, it is unclear whether these roles correspond to distinct γδ subsets or to a homogeneous population of cells exerting context-dependent functions. Here, by cross-organ multimodal single-cell profiling, we reveal that various mouse tissues harbor unique site-adapted γδ subsets. Epidermal and intestinal intraepithelial γδ T cells are transcriptionally homogeneous and exhibit epigenetic hallmarks of functional diversity. Through parabiosis experiments, we uncovered cellular states associated with cytotoxicity, innate-like rapid IFN-γ production and tissue repair functions displaying tissue residency hallmarks. Notably, our observations nuance the link between IL-17-producing γδ T cells and tissue residency. Moreover, transcriptional programs associated with tissue-resident γδ T cells are analogous to those of CD8+ tissue-resident memory T cells. Altogether, this study provides the first multimodal landscape of tissue-adapted γδ T cells, revealing heterogeneity, lineage relationships and their tissue residency program.
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| Overall design |
To identify and compare various subsets of γδ T cells present across different tissues, we took a single-cell multimodal approach and sorted gd T cells from lymph nodes, spleen, liver, lung, skin, small and large intestine using flow cytometry. Sorted cells were subjected to single-cell sequencing using two different approaches. In the first approach, γδ T cells from different organs were barcoded with distinct oligonucleotide-conjugated antibodies as well as 26 other antibodies. The transcriptomes and epitopes were simultaneously profiled using single-cell RNA sequencing (scRNA-seq) and TotalSeq, respectively. In the second approach, simultaneous single-nucleus RNA sequencing (snRNA-seq) and assay for transposase-accessible chromatin using sequencing (scATAC-seq) were performed on pooled γδ T cells from different organs without sample barcoding. Furthermore, simultaneous profiling of RNA and gamma delta T cell receptor (TCR) profiling was also performed at a single-cell resolution.
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| Web link |
https://www.nature.com/articles/s41590-023-01710-y
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| Contributor(s) |
Sagar - |
| Citation(s) |
38177282 |
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| Submission date |
Jan 09, 2023 |
| Last update date |
Jan 05, 2024 |
| Contact name |
Sagar - |
| E-mail(s) |
sagar@uniklinik-freiburg.de
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| Organization name |
University Medical Center Freiburg
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| Department |
Department of Internal Medicine II
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| Lab |
Sagar
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| Street address |
Hugstetter Straße 55
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| City |
Freiburg |
| ZIP/Postal code |
79106 |
| Country |
Germany |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (21)
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| GSM6923614 |
gdTcells, mRNA-derived library DEC_GD_GEX |
| GSM6923615 |
gdTcells, HTO-derived library DEC_GD_HTO |
| GSM6923616 |
gdTcells, mRNA-derived library OCT_GD_GEX |
| GSM6923617 |
gdTcells, HTO and ADT-derived library OCT_GD_HTO_ADT |
| GSM6923618 |
gdTcells, mRNA-derived library parabiosis_circulating_p1_2_2_GEX |
| GSM6923619 |
gdTcells, HTO-derived library parabiosis_circulating_p1_2_2_HTO |
| GSM6923620 |
gdTcells, mRNA-derived library parabiosis_circulating_p2_1_1_GEX |
| GSM6923621 |
gdTcells, HTO-derived library parabiosis_circulating_p2_1_1_HTO |
| GSM6923622 |
gdTcells, mRNA-derived library parabiosis_resident_p1_1_1_GEX |
| GSM6923623 |
gdTcells, HTO-derived library parabiosis_resident_p1_1_1_HTO |
| GSM6923624 |
gdTcells, mRNA-derived library parabiosis_resident_p2_2_2_GEX |
| GSM6923625 |
gdTcells, HTO-derived library parabiosis_resident_p2_2_2_HTO |
| GSM6923626 |
gdTcells, Open chromatin-derived library MULTIOME_MPI_ATAC_Lib1 |
| GSM6923627 |
gdTcells, mRNA-derived library MULTIOME_MPI_GEX_Library |
| GSM6923628 |
gdTcells, Open chromatin-derived library MULTIOME_Paris_ATAC_Lib1 |
| GSM6923629 |
gdTcells, Open chromatin-derived library MULTIOME_Paris_ATAC_Lib2 |
| GSM6923630 |
gdTcells, mRNA-derived library MULTIOME_Paris_GEX_Lib_1 |
| GSM6923631 |
gdTcells, mRNA-derived library MULTIOME_Paris_GEX_Lib_2 |
| GSM7720293 |
gdTcells, mRNA-derived library, VDJ5PGD_GEX |
| GSM7720294 |
gdTcells, HTO-derived library, VDJ5PGD_HASH |
| GSM7720295 |
gdTcells, gamma-delta TCR RNA-derived library, VDJ5PGD_TCR |
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| Relations |
| BioProject |
PRJNA922136 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE222454_DEC_GD_barcodes.tsv.gz |
42.1 Kb |
(ftp)(http) |
TSV |
| GSE222454_DEC_GD_features.tsv.gz |
284.2 Kb |
(ftp)(http) |
TSV |
| GSE222454_DEC_GD_matrix.mtx.gz |
41.6 Mb |
(ftp)(http) |
MTX |
| GSE222454_MULTIOME_MPI_filtered_feature_bc_matrix.h5 |
206.7 Mb |
(ftp)(http) |
H5 |
| GSE222454_MULTIOME_Paris_Lib1_filtered_feature_bc_matrix.h5 |
81.3 Mb |
(ftp)(http) |
H5 |
| GSE222454_MULTIOME_Paris_Lib2_filtered_feature_bc_matrix.h5 |
92.2 Mb |
(ftp)(http) |
H5 |
| GSE222454_OCT_GD_barcodes.tsv.gz |
69.6 Kb |
(ftp)(http) |
TSV |
| GSE222454_OCT_GD_features.tsv.gz |
284.4 Kb |
(ftp)(http) |
TSV |
| GSE222454_OCT_GD_matrix.mtx.gz |
92.6 Mb |
(ftp)(http) |
MTX |
| GSE222454_RAW.tar |
270.0 Kb |
(http)(custom) |
TAR (of CSV) |
| GSE222454_VDJ5PGD_barcodes.tsv.gz |
93.8 Kb |
(ftp)(http) |
TSV |
| GSE222454_VDJ5PGD_features.tsv.gz |
284.2 Kb |
(ftp)(http) |
TSV |
| GSE222454_VDJ5PGD_matrix.mtx.gz |
149.0 Mb |
(ftp)(http) |
MTX |
| GSE222454_parabiosis_circulating_p1_2_2_barcodes.tsv.gz |
42.7 Kb |
(ftp)(http) |
TSV |
| GSE222454_parabiosis_circulating_p1_2_2_features.tsv.gz |
284.3 Kb |
(ftp)(http) |
TSV |
| GSE222454_parabiosis_circulating_p1_2_2_matrix.mtx.gz |
48.4 Mb |
(ftp)(http) |
MTX |
| GSE222454_parabiosis_circulating_p2_1_1_barcodes.tsv.gz |
28.6 Kb |
(ftp)(http) |
TSV |
| GSE222454_parabiosis_circulating_p2_1_1_features.tsv.gz |
284.3 Kb |
(ftp)(http) |
TSV |
| GSE222454_parabiosis_circulating_p2_1_1_matrix.mtx.gz |
27.6 Mb |
(ftp)(http) |
MTX |
| GSE222454_parabiosis_resident_p1_1_1_barcodes.tsv.gz |
88.3 Kb |
(ftp)(http) |
TSV |
| GSE222454_parabiosis_resident_p1_1_1_features.tsv.gz |
284.3 Kb |
(ftp)(http) |
TSV |
| GSE222454_parabiosis_resident_p1_1_1_matrix.mtx.gz |
96.4 Mb |
(ftp)(http) |
MTX |
| GSE222454_parabiosis_resident_p2_2_2_barcodes.tsv.gz |
65.8 Kb |
(ftp)(http) |
TSV |
| GSE222454_parabiosis_resident_p2_2_2_features.tsv.gz |
284.3 Kb |
(ftp)(http) |
TSV |
| GSE222454_parabiosis_resident_p2_2_2_matrix.mtx.gz |
67.7 Mb |
(ftp)(http) |
MTX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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