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The landscape of multiscale transcriptomic networks and key regulators in Parkinson’s disease

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  • Qian Wang

    (Department of Neurology and Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai
    Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai
    Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai
    Icahn Institute of Genomics and Multi-scale Biology, Icahn School of Medicine at Mount Sinai)

  • Yuanxi Zhang

    (Department of Neurology and Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Minghui Wang

    (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai
    Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai
    Icahn Institute of Genomics and Multi-scale Biology, Icahn School of Medicine at Mount Sinai)

  • Won-Min Song

    (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai
    Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai
    Icahn Institute of Genomics and Multi-scale Biology, Icahn School of Medicine at Mount Sinai)

  • Qi Shen

    (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai
    Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai
    Icahn Institute of Genomics and Multi-scale Biology, Icahn School of Medicine at Mount Sinai)

  • Andrew McKenzie

    (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai
    Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai
    Icahn Institute of Genomics and Multi-scale Biology, Icahn School of Medicine at Mount Sinai)

  • Insup Choi

    (Department of Neurology and Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Xianxiao Zhou

    (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai
    Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai
    Icahn Institute of Genomics and Multi-scale Biology, Icahn School of Medicine at Mount Sinai)

  • Ping-Yue Pan

    (Department of Neurology and Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Zhenyu Yue

    (Department of Neurology and Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Bin Zhang

    (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai
    Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai
    Icahn Institute of Genomics and Multi-scale Biology, Icahn School of Medicine at Mount Sinai)

Abstract

Genetic and genomic studies have advanced our knowledge of inherited Parkinson’s disease (PD), however, the etiology and pathophysiology of idiopathic PD remain unclear. Herein, we perform a meta-analysis of 8 PD postmortem brain transcriptome studies by employing a multiscale network biology approach to delineate the gene-gene regulatory structures in the substantia nigra and determine key regulators of the PD transcriptomic networks. We identify STMN2, which encodes a stathmin family protein and is down-regulated in PD brains, as a key regulator functionally connected to known PD risk genes. Our network analysis predicts a function of human STMN2 in synaptic trafficking, which is validated in Stmn2-knockdown mouse dopaminergic neurons. Stmn2 reduction in the mouse midbrain causes dopaminergic neuron degeneration, phosphorylated α-synuclein elevation, and locomotor deficits. Our integrative analysis not only begins to elucidate the global landscape of PD transcriptomic networks but also pinpoints potential key regulators of PD pathogenic pathways.

Suggested Citation

  • Qian Wang & Yuanxi Zhang & Minghui Wang & Won-Min Song & Qi Shen & Andrew McKenzie & Insup Choi & Xianxiao Zhou & Ping-Yue Pan & Zhenyu Yue & Bin Zhang, 2019. "The landscape of multiscale transcriptomic networks and key regulators in Parkinson’s disease," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13144-y
    DOI: 10.1038/s41467-019-13144-y
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    Cited by:

    1. Sebastian Schmidt & Malte D. Luecken & Dietrich Trümbach & Sina Hembach & Kristina M. Niedermeier & Nicole Wenck & Klaus Pflügler & Constantin Stautner & Anika Böttcher & Heiko Lickert & Ciro Ramirez-, 2022. "Primary cilia and SHH signaling impairments in human and mouse models of Parkinson’s disease," Nature Communications, Nature, vol. 13(1), pages 1-25, December.
    2. Stergios Tsartsalis & Hannah Sleven & Nurun Fancy & Frank Wessely & Amy M. Smith & Nanet Willumsen & To Ka Dorcas Cheung & Michal J. Rokicki & Vicky Chau & Eseoghene Ifie & Combiz Khozoie & Olaf Ansor, 2024. "A single nuclear transcriptomic characterisation of mechanisms responsible for impaired angiogenesis and blood-brain barrier function in Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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