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E-GEOD-5580 - Transcription profiling of human blood leukocytes and T-cells

Status
Submitted on 23 August 2006, released on 13 June 2008, last updated on 27 March 2012
Organism
Homo sapiens
Samples (42)
Array (1)
Protocols (2)
Description
Monitoring genome-wide, cell-specific responses to human disease, although challenging, holds great promise for medicine’s future. Patients with injury severe enough to develop multiple organ dysfunction syndrome (MODS) are known to have multiple immune derangements, including T-cell apoptosis and anergy combined with depressed monocyte antigen presentation. Genome-wide expression analysis of highly-enriched circulating leukocyte subpopulations, combined with cell-specific pathway analyses, offers a previously unavailable opportunity to discover novel leukocyte regulatory networks in critically injured patients. Severe injury induced significant changes in the T-cell, monocyte, and total leukocyte transcriptome, with only 12% of these genomic changes common to all three cell populations. T-cell-specific pathway analyses identified increased gene expression of several novel inhibitory receptors (PD-1, CD152, NRP-1, Lag3), and concomitant decreases in stimulatory receptors (CD28, CD4, IL-2R). Functional analysis of T-cells and monocytes confirmed reduced T-cell proliferation and increased cell surface expression of negative signaling receptors paired with decreased monocyte costimulation ligands. Thus, genome-wide expression from highly-enriched cell populations combined with knowledge-based pathway analyses leads to the identification of novel regulatory networks differentially expressed in injured patients. Importantly, application of cell separation, genome-wide expression, and cell specific pathway analyses can be used to discover novel pathway alterations in human disease. Experiment Overall Design: Type of experiment: Gene expression profiling of circulating total blood Experiment Overall Design: leukocytes, T-Cells, and Monocytes in severe trauma patients and healthy subjects. Experiment Overall Design: Experimental factors: Healthy subjects, 7 severely traumatized patients Experiment Overall Design: and 7 healthy subjects for transcriptome analysis. Venous blood samples Experiment Overall Design: were collected. Total blood leukocytes were isolated, and T-cell and Experiment Overall Design: monocyte populations were obtained from two subsequent aliquots of the Experiment Overall Design: leukocytes. Total leukocytes, enriched T-cells, and enriched monocytes were analyzed using Affymetrix GeneChip arrays. Experiment Overall Design: Number of hybridizations: 42 Human U133A GeneChip arrays (Affymetrix)
Experiment types
transcription profiling by array, unknown experiment type
Contact
Citation
Cell-specific expression and pathway analyses reveal alterations in trauma-related human T cell and monocyte pathways. Krzysztof Laudanski, Carol Miller-Graziano, Wenzhong Xiao, Michael N Mindrinos, Daniel R Richards, Asit De, Lyle L Moldawer, Ronald V Maier, Paul Bankey, Henry V Baker, Bernard H Brownstein, J Perren Cobb, Steve E Calvano, Ronald W Davis, Ronald G Tompkins. Proc Natl Acad Sci U S A 103(42):15564-9 (2006)
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-5580.idf.txt
Sample and data relationshipE-GEOD-5580.sdrf.txt
Raw data (1)E-GEOD-5580.raw.1.zip
Processed data (1)E-GEOD-5580.processed.1.zip
Array designA-AFFY-33.adf.txt
R ExpressionSetE-GEOD-5580.eSet.r
Links