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Series GSE112731 Query DataSets for GSE112731
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
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.
 
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.
 
Contributor(s) DiSpirito JR, Benoist C, Mathis D
Citation(s) 30217811
Submission date Apr 05, 2018
Last update date Mar 25, 2019
Contact name CBDM Lab
E-mail(s) cbdm@hms.harvard.edu
Phone 617-432-7747
Organization name Harvard Medical School
Department Microbiology and Immunobiology
Lab CBDM
Street address 77 Avenue Louis Pasteur
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (16)
GSM3082685 Treg_ATAC_VAT_1
GSM3082686 Treg_ATAC_VAT_2
GSM3082687 Treg_ATAC_Muscle_1
Relations
BioProject PRJNA448878
SRA SRP137672

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MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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
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Raw data are available in SRA
Processed data are available on Series record

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