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Gene set enrichment analysis identifies LIF as a negative regulator of human Th2 cell differentiation.

Ullah U, Tripathi P, Lahesmaa R, Rao KV - Sci Rep (2012)

Bottom Line: In this study we show that IL-4 is crucial during reinforcement window of human Th2 differentiation for optimal Th2 development.We have also shown here that during this stage, IL-4 helps in cellular decision-making process of differentiation versus proliferation.This approach can be generalized to analyze "omics" data to identify key regulatory modules.

View Article: PubMed Central - PubMed

Affiliation: Immunology Group International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India.

ABSTRACT
In this study we show that IL-4 is crucial during reinforcement window of human Th2 differentiation for optimal Th2 development. We have also shown here that during this stage, IL-4 helps in cellular decision-making process of differentiation versus proliferation. We have combined computational and experimental methods to analyze Th2 transcription network to name novel players of the process of Th2 differentiation. Here we report that LIF through STAT3 negatively regulates Th2 differentiation. This approach can be generalized to analyze "omics" data to identify key regulatory modules.

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Related in: MedlinePlus

Gene Ontology of IL-4 dependent upregulated genes.Enriched gene ontology (GO) categories in IL-4 dependent upregulated genes using human housekeeping genes as a background set. Blue bar represents actual enriched number of genes while red bar represents expected enrichment by chance.
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f2: Gene Ontology of IL-4 dependent upregulated genes.Enriched gene ontology (GO) categories in IL-4 dependent upregulated genes using human housekeeping genes as a background set. Blue bar represents actual enriched number of genes while red bar represents expected enrichment by chance.

Mentions: IL-4 dependent genes were identified using the methodology detailed in the method section. The exercise resulted in identification of 128 IL-4 dependent upregulated genes, and 151 IL-4 dependent down regulated genes. The list of these up and down regulated genes along with their functions, as described in Biobase Knowledge Library, (BKL) (www.biobase-international.com) are given as Supplementary Table 2 and 3 respectively. To identify if any Gene Ontology (GO) classes are enriched in any of these two differentially expressed gene sets, GO analysis was performed on “Explain Analysis System” of Biobase (TRANSFAC) database. Many GO classes were enriched in the upregulated gene set including cell activation, cell differentiation and regulation of T cell anergy at the p value threshold of 0.01 as shown in Figure 2. However at this cut off only two GO classes were enriched in down regulated gene set (Developmental process and Multi-cellular organismal process) and the overall low enrichment was retained even at p value threshold of 0.1. The observed difference in the enrichment in the two classes may partly be attributed to the ability of IL-4 to specifically upregulate target genes.


Gene set enrichment analysis identifies LIF as a negative regulator of human Th2 cell differentiation.

Ullah U, Tripathi P, Lahesmaa R, Rao KV - Sci Rep (2012)

Gene Ontology of IL-4 dependent upregulated genes.Enriched gene ontology (GO) categories in IL-4 dependent upregulated genes using human housekeeping genes as a background set. Blue bar represents actual enriched number of genes while red bar represents expected enrichment by chance.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376453&req=5

f2: Gene Ontology of IL-4 dependent upregulated genes.Enriched gene ontology (GO) categories in IL-4 dependent upregulated genes using human housekeeping genes as a background set. Blue bar represents actual enriched number of genes while red bar represents expected enrichment by chance.
Mentions: IL-4 dependent genes were identified using the methodology detailed in the method section. The exercise resulted in identification of 128 IL-4 dependent upregulated genes, and 151 IL-4 dependent down regulated genes. The list of these up and down regulated genes along with their functions, as described in Biobase Knowledge Library, (BKL) (www.biobase-international.com) are given as Supplementary Table 2 and 3 respectively. To identify if any Gene Ontology (GO) classes are enriched in any of these two differentially expressed gene sets, GO analysis was performed on “Explain Analysis System” of Biobase (TRANSFAC) database. Many GO classes were enriched in the upregulated gene set including cell activation, cell differentiation and regulation of T cell anergy at the p value threshold of 0.01 as shown in Figure 2. However at this cut off only two GO classes were enriched in down regulated gene set (Developmental process and Multi-cellular organismal process) and the overall low enrichment was retained even at p value threshold of 0.1. The observed difference in the enrichment in the two classes may partly be attributed to the ability of IL-4 to specifically upregulate target genes.

Bottom Line: In this study we show that IL-4 is crucial during reinforcement window of human Th2 differentiation for optimal Th2 development.We have also shown here that during this stage, IL-4 helps in cellular decision-making process of differentiation versus proliferation.This approach can be generalized to analyze "omics" data to identify key regulatory modules.

View Article: PubMed Central - PubMed

Affiliation: Immunology Group International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India.

ABSTRACT
In this study we show that IL-4 is crucial during reinforcement window of human Th2 differentiation for optimal Th2 development. We have also shown here that during this stage, IL-4 helps in cellular decision-making process of differentiation versus proliferation. We have combined computational and experimental methods to analyze Th2 transcription network to name novel players of the process of Th2 differentiation. Here we report that LIF through STAT3 negatively regulates Th2 differentiation. This approach can be generalized to analyze "omics" data to identify key regulatory modules.

Show MeSH
Related in: MedlinePlus