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Series GSE42573 Query DataSets for GSE42573
Status Public on Jul 01, 2014
Title In vivo LPS responses in murine splenic CD8 and CD11b DC subsets
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Background: Dendritic cells (DCs) are critical for regulating CD4 and CD8 T cell immunity, controlling Th1, Th2, and Th17 bias, generating inducible Tregs, and inducing tolerance. Multiple DC subsets have been identified in the mouse that are thought to have evolved to control these different immune outcomes. However, how these subsets differentially respond to inflammatory and/or tolerogenic signals in order to accomplish their divergent functionality remains unclear. Results: We analysed the responses of murine, splenic CD8 and CD11b DC subsets to in-vivo stimulation with lipopolysaccharide using RNA-Seq and systems biology approaches and observed responses are highly subset-specific. We reanalysed multiple datasets from the literature and show that these subset responses are obscured when analysing signaling at the population level. We show that the subset-specificity is due to the unique regulation of distinct TLR4 pathway modulators that ‘fine-tune’ a common TLR4 cascade rather and not due to major differences in signaling pathways or transcription factors. Conclusions: We propose the Pathway Modulation Model wherein common signaling pathways are regulated by unique sets of modulators allowing for distinct immune responses in closely related DC subsets. We extend these observations using analagous datasets from the literature and show that our model provides a global mechanism for generating cell subset-specific signaling in multiple subpopulations in mouse and man.
Overall design Splenic CD8 and CD11b DC subsets from LPS stimulated (10 pooled animals) and Control (5 pooled animals) mice were analysed by RNA-Seq.
Contributor(s) Hancock DG, Shklovskaya E, Guy TV, Falsafi R, Fjell CD, Ritchie W, Hancock RE, Fazekas de St Groth B
Citation(s) 24949855
Submission date Nov 28, 2012
Last update date May 15, 2019
Contact name David Graeme Hancock
Organization name Centenary Institute
Street address Building 93, RPAH, Missenden Road
City Camperdown
State/province NSW
ZIP/Postal code 2050
Country Australia
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (4)
GSM1045344 CD8_DC_Ctrl
GSM1045345 CD8_DC_LPS
GSM1045346 CD11b_DC_Ctrl
BioProject PRJNA182314
SRA SRP017333

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Supplementary file Size Download File type/resource
GSE42573_RAW.tar 490.0 Kb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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