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Role of astroglia in Down’s syndrome revealed by patient-derived human-induced pluripotent stem cells

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  • Chen Chen

    (School of Medicine, University of California
    Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children
    Institute of Neurology, Tianjin General Hospital, Tianjin Medical University)

  • Peng Jiang

    (School of Medicine, University of California
    Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children)

  • Haipeng Xue

    (University of Texas Health Science Center at Houston
    Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston
    University of California, San Diego
    Center for Regenerative Medicine, The Scripps Research Institute)

  • Suzanne E. Peterson

    (Center for Regenerative Medicine, The Scripps Research Institute)

  • Ha T. Tran

    (Center for Regenerative Medicine, The Scripps Research Institute)

  • Anna E. McCann

    (Center for Regenerative Medicine, The Scripps Research Institute
    Present address: Department of Biology, University of Washington, Seattle, Washington 98195, USA)

  • Mana M. Parast

    (University of California, San Diego)

  • Shenglan Li

    (University of Texas Health Science Center at Houston
    Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston)

  • David E. Pleasure

    (Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children)

  • Louise C. Laurent

    (University of California, San Diego
    Center for Regenerative Medicine, The Scripps Research Institute)

  • Jeanne F. Loring

    (University of California, San Diego
    Center for Regenerative Medicine, The Scripps Research Institute)

  • Ying Liu

    (University of Texas Health Science Center at Houston
    Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston
    University of California, San Diego
    Center for Regenerative Medicine, The Scripps Research Institute)

  • Wenbin Deng

    (School of Medicine, University of California
    Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children)

Abstract

Down’s syndrome (DS), caused by trisomy of human chromosome 21, is the most common genetic cause of intellectual disability. Here we use induced pluripotent stem cells (iPSCs) derived from DS patients to identify a role for astrocytes in DS pathogenesis. DS astroglia exhibit higher levels of reactive oxygen species and lower levels of synaptogenic molecules. Astrocyte-conditioned medium collected from DS astroglia causes toxicity to neurons, and fails to promote neuronal ion channel maturation and synapse formation. Transplantation studies show that DS astroglia do not promote neurogenesis of endogenous neural stem cells in vivo. We also observed abnormal gene expression profiles from DS astroglia. Finally, we show that the FDA-approved antibiotic drug, minocycline, partially corrects the pathological phenotypes of DS astroglia by specifically modulating the expression of S100B, GFAP, inducible nitric oxide synthase, and thrombospondins 1 and 2 in DS astroglia. Our studies shed light on the pathogenesis and possible treatment of DS by targeting astrocytes with a clinically available drug.

Suggested Citation

  • Chen Chen & Peng Jiang & Haipeng Xue & Suzanne E. Peterson & Ha T. Tran & Anna E. McCann & Mana M. Parast & Shenglan Li & David E. Pleasure & Louise C. Laurent & Jeanne F. Loring & Ying Liu & Wenbin D, 2014. "Role of astroglia in Down’s syndrome revealed by patient-derived human-induced pluripotent stem cells," Nature Communications, Nature, vol. 5(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5430
    DOI: 10.1038/ncomms5430
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    Cited by:

    1. Hyosung Kim & Kun Leng & Jinhee Park & Alexander G. Sorets & Suil Kim & Alena Shostak & Rebecca J. Embalabala & Kate Mlouk & Ketaki A. Katdare & Indigo V. L. Rose & Sarah M. Sturgeon & Emma H. Neal & , 2022. "Reactive astrocytes transduce inflammation in a blood-brain barrier model through a TNF-STAT3 signaling axis and secretion of alpha 1-antichymotrypsin," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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