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Series GSE38909 Query DataSets for GSE38909
Status Public on Jul 01, 2012
Title Transcriptional profiling analysis of pre-selected DP thymocytes in response to positive and negative selection signals
Organism Mus musculus
Experiment type Expression profiling by array
Summary Sustained Ca2+ entry into CD4+CD8+ double-positive thymocytes is required for positive selection. We identified a voltage-gated Na+ channel (VGSC), essential for positive selection of CD4+ T cells. Pharmacological inhibition of VGSC activity inhibited sustained Ca2+ influx induced by positive-selecting ligands and in vitro positive selection of CD4+ but not CD8+ T cells. In vivo shRNA knockdown of Scn5a specifically inhibited positive selection of CD4+ T cells. Ectopic expression of VGSC in peripheral AND CD4+ T cells bestowed the ability to respond to a positively selecting ligand, directly demonstrating VGSC expression was responsible for increased sensitivity. Thus active VGSCs in thymocytes provides a mechanism by which a weak positive selecting signal can induce sustained Ca2+ signals required for CD4+ T cell development.
 
Overall design Pre-selected AND DP thymocytes were stimulated with plate bound peptide-loaded I-Ek Ig dimers. Genes were differentially regulated by positive and negative selection signals.
The goal of this study is to identify ion-channel related genes critical for thymic positive selection, given the sustained Ca2+ entry into double positive thymocytes is required for positive selection. Total RNA of pre-selected AND thymocytes stimulated with I-Ek Ig dimers loaded with the positively-selecting peptide gp250, the negatively-selecting agonist peptide MCC, or the non-selecting control peptide Hb were used for the transcriptional profiling analysis. We found 28 genes were differentially down-regulated by MCC stimulation but upregulated by gp250 stimulation. One of them, scn4b, was ion-channel related.
 
Contributor(s) Lo W, Allen PM
Citation(s) 22842345
Submission date Jun 25, 2012
Last update date Jun 14, 2018
Contact name Wan-Lin Lo
Organization name Washington University in St Louis
Street address 425 S Euclid Ave, campus box 8118
City Saint Louis
ZIP/Postal code 63110
Country USA
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (6)
GSM952008 AND.Rag1-/-H-2d DP thymocytes_MCC/I-Ek stimulation_rep1
GSM952009 AND.Rag1-/-H-2d DP thymocytes_gp250/I-Ek stimulation_rep1
GSM952010 AND.Rag1-/-H-2d DP thymocytes_Hb/I-Ek stimulation_rep1
Relations
BioProject PRJNA169320

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE38909_RAW.tar 3.1 Mb (http)(custom) TAR
GSE38909_non-normalized_matrix.txt.gz 1.1 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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