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Series GSE143972 Query DataSets for GSE143972
Status Public on Aug 27, 2020
Title Maintenance DNA methylation is essential for regulatory T cell development and stability of suppressive function [gene expression/RNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Regulatory T (Treg) cells require Foxp3 expression and induction of a specific DNA hypomethylation signature during development, after which Treg cells persist as a self-renewing population that regulates immune system activation. Whether maintenance DNA methylation is required for Treg cell lineage development and stability and how methylation patterns are maintained during lineage self-renewal remain unclear. Here, we demonstrate that the epigenetic regulator Uhrf1 is essential for maintenance of methyl-DNA marks that stabilize Treg cellular identity by repressing effector T cell transcriptional programs. Constitutive and induced deficiency of Uhrf1 within Foxp3+ cells resulted in global yet non-uniform loss of DNA methylation, derepression of inflammatory transcriptional programs, destabilization of the Treg cell lineage, and spontaneous inflammation. These findings support a paradigm in which maintenance DNA methylation is required in distinct regions of the Treg cell genome for both lineage establishment and stability of identity and suppressive function.
 
Overall design Treg cells (CD25hiFoxp3-YFP+) from 8-week-old female Uhrf1fl/flFoxp3+/YFP-Cre (Uhrf1 chimeric knockout) or Uhrf1+/+Foxp3YFP-Cre/YFP-Cre (control) mice with n = 4 biological replicates per group; labeled Treg cells (Foxp3-GFP+tdTomato+), ex-Foxp3 cells (Foxp3-GFP–tdTomato+), and post-tamoxifen Treg cells (Foxp3-GFP+tdTomato–) from Uhrf1fl/flFoxp3GFP-CreERT2Rosa26SorCAG-tdTomato (a.k.a. iUhrf1fl/fl) or Uhrf1+/+Foxp3GFP-CreERT2Rosa26SorCAG-tdTomato (a.k.a iUhrf1+/+ control) mice with n = 6 (iUhrf1fl/fl) and 5 (iUhrf1+/+) biological replicates per cell type in 8-week-old mice that received tamoxifen chow for 2 weeks followed by standard chow for 4 weeks
 
Contributor(s) Singer BD
Citation(s) 32897881
NIH grant(s)
Grant ID Grant title Affiliation Name
T32 HL076139 Training Program In Lung Sciences NORTHWESTERN UNIVERSITY AT CHICAGO KAREN M RIDGE
T32 HL076139 Training Program In Lung Sciences NORTHWESTERN UNIVERSITY AT CHICAGO Jacob I Sznajder
F32 HL151127 Determinants of age-related regulatory T cell function during influenza A virus-induced lung injury. NORTHWESTERN UNIVERSITY AT CHICAGO Luisa Morales-Nebreda
T32 GM008152 Medical Scientist Training Program NORTHWESTERN UNIVERSITY AT CHICAGO Hossein Ardehali
K08 HL128867 Regulatory T cell Uhrf1 and DNA methylation in repair of acute lung injury NORTHWESTERN UNIVERSITY AT CHICAGO Benjamin David Singer
R01 HL149883 Mechanisms of regulatory T cell-mediated recovery from severe influenza A virus infection NORTHWESTERN UNIVERSITY AT CHICAGO Benjamin David Singer
U19 AI135964 Successful Clinical Response In Pneumonia Therapy (SCRIPT) Systems Biology Center NORTHWESTERN UNIVERSITY AT CHICAGO RICHARD G WUNDERINK
Submission date Jan 21, 2020
Last update date Sep 09, 2020
Contact name Benjamin D. Singer
E-mail(s) benjamin-singer@northwestern.edu
Organization name Northwestern University Feinberg School of Medicine
Street address 303 E. Superior St., Simpson Querrey 5th floor
City Chicago
State/province Illinois
ZIP/Postal code 60611
Country USA
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (41)
GSM4277467 Chimera_exp_control_01 (RNA-seq)
GSM4277468 Chimera_exp_control_02 (RNA-seq)
GSM4277469 Chimera_exp_control_03 (RNA-seq)
This SubSeries is part of SuperSeries:
GSE143974 Maintenance DNA methylation is essential for regulatory T cell development and stability of suppressive function
Relations
BioProject PRJNA602403
SRA SRP243617

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Supplementary file Size Download File type/resource
GSE143972_seqmonk_raw_counts.txt.gz 1.3 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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