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GEO help: Mouse over screen elements for information. |
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Status |
Public on Sep 25, 2018 |
Title |
Molecular diversification of regulatory T cells in non-lymphoid tissues |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Foxp3+CD4+ regulatory T (Treg) cells accumulate in certain non-lymphoid tissues, where they control diverse aspects of organ homeostasis, partly via a direct impact on neighboring non-immune cells. Populations of tissue-Tregs, as they have been termed, have transcriptomes distinct from those of their counterparts in lymphoid organs and other non-lymphoid tissues. Exploiting recent advances in profiling the chromatin accessibility and gene expression of rare cell populations, we examined the diversification of Tregs in visceral-adipose tissue, skeletal muscle and the colon vis-à-vis lymphoid organs from the same individuals. The unique transcriptomes of the various tissue-Treg populations reflected layering of tissue-restricted stretches of accessibility over a “primed” landscape of sites already open in the spleen, where they were tagged by super-enhancers and “bivalent” histone marks of transcriptional activation and repression. Tissue-restricted chromatin accessibility and gene expression correlated with the binding motifs of a small number of transcription-factor (TF) families repeatedly enriched across the various non-lymphoid tissues. However, a bioinformatically and experimentally validated transcriptional network constructed using a combination of chromatin-accessibility and single-cell transcriptomic data predicted usage of different TF-family members in the different tissues. The network analysis also revealed that tissue-restricted and ubiquitously acting TFs were integrated into feed-forward loops to enforce tissue-specific gene expression in non-lymphoid-tissue Treg cells. Overall, this study provides a framework for understanding the epigenetic dynamics of T cells operating in non-lymphoid tissues, which should inform strategies for specifically targeting them.
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Overall design |
Tregs were isolated from visceral-adipose tissue, injured skeletal muscle, and colonic lamina propria. For each tissue, Tregs were also isolated from the spleen at the time of harvest and ATAC-seq (Assay for Transposase-Accessible Chromatin) was performed. The experiment was done in duplicates for all populations. Each VAT, muscle, colon sample was paired with a spleen sample taken from the same animal. For example, Treg_ATAC_VAT_1 and Treg_ATAC_Spl_wVAT_1 come from the same animal. Mouse IDs are also provided so that samples can be easily matched by mouse.
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Contributor(s) |
DiSpirito JR, Benoist C, Mathis D |
Citation(s) |
30217811 |
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Submission date |
Apr 05, 2018 |
Last update date |
Mar 25, 2019 |
Contact name |
CBDM Lab |
E-mail(s) |
cbdm@hms.harvard.edu
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Phone |
617-432-7747
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Organization name |
Harvard Medical School
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Department |
Microbiology and Immunobiology
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Lab |
CBDM
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Street address |
77 Avenue Louis Pasteur
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City |
Boston |
State/province |
MA |
ZIP/Postal code |
02215 |
Country |
USA |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (16)
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Relations |
BioProject |
PRJNA448878 |
SRA |
SRP137672 |
Supplementary file |
Size |
Download |
File type/resource |
GSE112731_Cln_Treg_merged_rep1.bw |
62.6 Mb |
(ftp)(http) |
BW |
GSE112731_Cln_Treg_merged_rep2.bw |
81.0 Mb |
(ftp)(http) |
BW |
GSE112731_Mus_Treg_rep1.bw |
138.8 Mb |
(ftp)(http) |
BW |
GSE112731_Mus_Treg_rep2.bw |
143.1 Mb |
(ftp)(http) |
BW |
GSE112731_Spl_wCln_Treg_rep1.bw |
61.6 Mb |
(ftp)(http) |
BW |
GSE112731_Spl_wCln_Treg_rep2.bw |
52.7 Mb |
(ftp)(http) |
BW |
GSE112731_Spl_wMus_Treg_rep1.bw |
154.1 Mb |
(ftp)(http) |
BW |
GSE112731_Spl_wMus_Treg_rep2.bw |
133.2 Mb |
(ftp)(http) |
BW |
GSE112731_Spl_wVAT_Treg_rep1.bw |
103.9 Mb |
(ftp)(http) |
BW |
GSE112731_Spl_wVAT_Treg_rep2.bw |
112.3 Mb |
(ftp)(http) |
BW |
GSE112731_Tissue_treg_ocr_75363.bed.gz |
576.5 Kb |
(ftp)(http) |
BED |
GSE112731_Vat_Treg_rep1.bw |
152.3 Mb |
(ftp)(http) |
BW |
GSE112731_Vat_Treg_rep2.bw |
147.5 Mb |
(ftp)(http) |
BW |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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