title: Early divergence of Th1 and Th2 transcriptomes involves a small core response and sets of transiently expressed genes.
abstract: Th cells can adopt a number of different phenotypes. We performed microarray-assisted mRNA profiling on antigen-stimulated, TCR transgenic murine splenocytes that were cultured in the presence of cytokines. Transcriptome snapshots of Th cells differentiating into Th1 and Th2 phenotypes were obtained at various time points. Principal component analysis shows that time since activation and Th skewing are the largest sources of variance (i.e. the largest contributing factors) in our profiling experiments. Divergence between the Th1 and Th2 phenotypes is established early and does not increase in terms of number of differential genes from day 1 to day 4 after stimulation. Notwithstanding the lack of further divergence between the Th1 and Th2 lineages, we show that gene expression is best described by a 'turnover' rather than a 'core response' model, although we find evidence for both. We identify clusters of skewed genes associated with early persistent ('core response') and late ('turnover') Th1 and Th2 gene expression. In addition to the classical Th genes, members of the Batf transcription factor family are differentially expressed in particular helper phenotypes, suggesting an important role for this family in Th-cell phenotype differentiation.
authors: Department of Virology, Erasmus MC, Rotterdam, The Netherlands; Theoretical Biology & Bioinformatics, Utrecht University, Utrecht, The Netherlands. h.j.vandenham@erasmusmc.nl
authors: Henk-Jan
authors: HJ
authors: van den Ham
authors: Leon
authors: L
authors: de Waal
authors: Fatiha
authors: F
authors: Zaaraoui-Boutahar
authors: Maarten
authors: M
authors: Bijl
authors: Wilfred F J
authors: WF
authors: van Ijcken
authors: Albert D M E
authors: AD
authors: Osterhaus
authors: Rob J
authors: RJ
authors: de Boer
authors: Arno C
authors: AC
authors: Andeweg
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D010641:Phenotype; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D013997:Time Factors; D059467:Transcriptome
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C431772:Batf protein, mouse