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Series GSE96538 Query DataSets for GSE96538
Status Public on Apr 06, 2018
Title Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Background: Regulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first-in-man trials of Treg transfer achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood.

Results: To gain a comprehensive and unbiased molecular understanding of FOXP3 induction, we performed time-series RNA sequencing (RNA-Seq) and proteomics profiling on the same samples during human iTreg differentiation. To enable the broad analysis of universal FOXP3-inducing pathways, we used five differentiation protocols in parallel. Integrative analysis of the transcriptome and proteome confirmed involvement of specific molecular processes, as well as overlap of a novel iTreg subnetwork with known Treg regulators and autoimmunity-associated genes. Importantly, we propose 37 novel molecules putatively involved in iTreg differentiation. Their relevance was validated by: a targeted shRNA screen confirming a functional role in FOXP3 induction; discriminant analyses classifying iTregs accordingly; and comparable expression in an independent novel iTreg RNA Seq data set.

Conclusion: The data generated by this novel approach facilitate understanding the molecular mechanisms underlying iTreg generation as well as the concomitant
changes in the transcriptome and proteome. Our results provide a reference map exploitable for future discovery of markers and drug candidates governing control of Tregs, which has important implications for the treatment of cancer, autoimmune and inflammatory diseases
 
Overall design Comparing the gene expression in activated CD4+ cells and iTreg differentiated cells in human. 10 time points, 3 biological replicates for each time point.
 
Contributor(s) Lahesmaa R, Wiendl H
Citation(s) 29730990
Submission date Mar 13, 2017
Last update date May 15, 2019
Contact name Sini Rautio
Organization name Aalto University
Street address Konemiehentie 2
City Espoo
ZIP/Postal code 02100
Country Finland
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (63)
GSM2535153 Thp_rep1
GSM2535154 Th0_0.5_rep1
GSM2535155 iTreg_0.5_rep1
Relations
BioProject PRJNA378953
SRA SRP101784

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Supplementary file Size Download File type/resource
GSE96538_rpkm.txt.gz 9.8 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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