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Interleukin-7 co-ordinates proliferation, differentiation and TCRA recombination during thymocyte β-selection

ABSTRACT: We used Illumina global gene expression profiling to compare IL7-regulated pathways in post-beta-selected DN3b and DN4 versus pre-beta-selected DN3a cell stages. We found that IL7 induced fewer genes in both DN3b and DN4 cells (800 and 300 respectively, versus 1800 in DN3a). We found several direct JAK/STAT target genes were significantly induced in all 3 stages. This group included Bcl2 and Cish, Socs2 and Socs3, feedback regulators of JAK-STAT signaling, as well as Pim1, Tfrc (Cd71) and Ccnd2. Thus, in addition to inducing survival genes, here we show that IL7 acutely regulates expression of trophic receptors and cell cycle regulators in pre- and post-beta-selection DN thymocytes.

ORGANISM(S): Mus musculus

PROVIDER: GSE63932 | GEO | 2015/02/05

SECONDARY ACCESSION(S): PRJNA269538

REPOSITORIES: GEO

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Project description:In order to explore the gene expression signature in essential thrombocythemia (ET) patients in relation to JAK2V617F mutational status, expression profiling in circulating granulocytes was performed. Twenty ET were studied by microarray analysis and the results were confirmed by real-time quantitative RT-PCR in 40 ET patients, not receiving cytoreductive treatment. A heterogeneous molecular signature characterized by two main gene expression patterns was found: one with an up-regulation of inflammatory genes related to neutrophil activation and thrombosis, and the other one with significantly lower expression of these genes. Supervised clustering analysis showed 30 genes differentially expressed between JAK2V617F-negative and JAK2V617F-positive ET patients. Among the JAK2V617F-negative, a set of 14 genes (CISH, C13orf18, CCL3, PIM1, MAFF, SOCS3, ID2, GADD45B, KLF5, TNF, LAMB3, HRH4, TAGAP and TRIB1) showed an abnormal expression pattern. In this group of patients CISH, SOCS2, SOCS3 and PIM1 genes, all involved in JAK-STAT signaling pathway, presented a lower expression,. A two-gene predictor model was built comprising FOSB and CISH genes, which were the best discriminators of JAK2V617F status. In conclusion, JAK2V617F-negative ET patients present a characteristic gene expression profile, different from JAK2V617F-positive patients. Other pathways besides JAK-STAT might be implicated in the pathophysiology of JAK2V617F-negative ET patients. Experiment Overall Design: Twenty ET were studied by microarray analysis and the results were confirmed by real-time quantitative RT-PCR in 40 ET patients. Microarray expression profiles were obtained using Whole Human Genome oligonucleotide microarrays (G4112A, Agilent Technologies, Palo Alto, CA). In each microarray experiment, RNA obtained from granulocytes from a single ET patient was compared with a pool of granulocyte RNAs from 10 healthy individuals. Duplicate hybridizations were performed for each comparison with dye-swapping to control.

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Interleukin-7 co-ordinates proliferation, differentiation and TCRA recombination during thymocyte β-selection

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