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Interleukin-7 (IL-7) and IL-7 splice variants affect differentiation of human neural progenitor cells

Genes & Immunity volume 11, pages 11–20 (2010)Cite this article

Abstract

Alternative splicing of pre-mRNA increases proteomic diversity, a crucial mechanism in defining tissue identity. We demonstrate differentially spliced interleukin (IL)-7 in distinct anatomic areas in the adult, in developing human brains and in normal human neuronal progenitor (NHNP) cells. IL-7c (c, the canonical form spanning all six exons) or its variants IL-7δ5, δ4 or δ4/5 were cloned and expressed as recombinant proteins. IL-7 and splice variants were able to shift the differentiation of NHNP cells as compared with the diluent control (P<0.01) defined by anti-β (III)-tubulin and glial fibrillary acidic protein expression, with different degrees (IL-7c>δ4/5>IL-7δ5); IL-7δ4 exhibited a significantly weaker potency. Differentiation was confirmed by transcriptome analysis of IL-7c-stimulated neural NHNP cells, resulting in 58 differentially expressed genes; some of these are involved in neural differentiation, for example, the developmentally regulated transcription factor krüppel-like factor 12, musashi 2, a translational regulator of cell fate or the sonic hedgehog receptor patch 1. This suggests that IL-7 influences neural development at a molecular level by participating in human brain architecture through glia cell formation: a paradigm that alternative splicing in cytokines, for example, for IL-7, has a physiological role in human organ development and progenitor cell differentiation.

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Acknowledgements

This work was supported from Karolinska Institutet and by a grant from Cancerfonden, Sweden to MM. We thank Dr Markus Frericks for help with gene expression analysis and Ali Moshfegh, Karolinska University Hospital (Affymetrix core facility lab). We are indebted to Hanni Höhn and Deshun Pan, Department of Med. Microbiology, University of Mainz, Germany for preparation of recombinant IL-7 proteins and to Michel Morre, Cytheris, Paris, France.

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Authors and Affiliations

  1. Group of Toxicology, Group of Epidemiology, Institut für Umweltmedizinische Forschung, Düsseldorf, Germany

    M Moors, J Abel, U Krämer & E Fritsche

  2. Microbiology, Tumor and Cell Biology and Smittskyddsinstitutet, Stockholm, Sweden

    N K Vudattu, L Rane & M J Maeurer

  3. Department of Anatomy, University of Rostock, Rostock, Germany

    N Ulfig

  4. Division of Neurotoxicology, Department of Neuroscience, Karolinska Institutet, Sweden

    M Moors & S Ceccatelli

  5. Department of Medicine, University of California, San Francisco, CA, USA

    V Seyfert-Margolies

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  1. M Moors
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Correspondence to M J Maeurer.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Moors, M., Vudattu, N., Abel, J. et al. Interleukin-7 (IL-7) and IL-7 splice variants affect differentiation of human neural progenitor cells. Genes Immun 11, 11–20 (2010). https://doi.org/10.1038/gene.2009.77

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