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In vivo phenotyping of Parkinson-specific stem cells reveals increased a-Synuclein levels but no spreading

Kathrin Hemmer, Lisa M. Smits, Silvia Bolognin, Jens C. Schwamborn
doi: https://doi.org/10.1101/140178
Kathrin Hemmer
Luxembourg Centre for Systems Biomedicine (LCSB), Developmental and Cellular Biology, University of Luxembourg, L-4367 Belvaux, Luxembourg
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Lisa M. Smits
Luxembourg Centre for Systems Biomedicine (LCSB), Developmental and Cellular Biology, University of Luxembourg, L-4367 Belvaux, Luxembourg
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Silvia Bolognin
Luxembourg Centre for Systems Biomedicine (LCSB), Developmental and Cellular Biology, University of Luxembourg, L-4367 Belvaux, Luxembourg
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Jens C. Schwamborn
Luxembourg Centre for Systems Biomedicine (LCSB), Developmental and Cellular Biology, University of Luxembourg, L-4367 Belvaux, Luxembourg
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Abstract

Parkinson′s disease is a progressive age-associated neurological disorder. One of the major neuropathological hallmarks of Parkinson’s disease is the appearance of protein aggregates, mainly consisting of the protein alpha-Synuclein. These aggregates have been described both in genetic as well as idiopathic forms of the disease. Currently, Parkinson’s disease patient-specific induced pluripotent stem cells (iPSCs) are mainly used for in vitro disease modeling or for experimental cell replacement approaches. Here, we demonstrate that these cells can be used for in vivo disease modeling. We show that Parkinson’s disease patient-specific, iPSC-derived neurons carrying the LRRK2-G2019S mutation show an upregulation of alpha-Synuclein after transplantation in the mouse brain. However, further investigations indicate that the increased human alpha-Synuclein levels fail to induce spreading or aggregation in the mouse brain. We therefore conclude that grafting of these cells into the mouse brain is suitable for cell autonomous in vivo disease modeling but has strong limitations beyond that. Furthermore, our results support the hypothesis that there might be a species barrier between human to mouse concerning alpha-Synuclein spreading.

  • Abbreviations

    α-SYN
    alpha-Synuclein,
    CC
    corpus callosum,
    iPSCs
    induced pluripotent stem cells,
    LB
    Lewy bodies,
    max
    maximum,
    NESCs
    neuroepithelial stem cells,
    ROI
    region of interest
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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    Posted May 19, 2017.
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    In vivo phenotyping of Parkinson-specific stem cells reveals increased a-Synuclein levels but no spreading
    Kathrin Hemmer, Lisa M. Smits, Silvia Bolognin, Jens C. Schwamborn
    bioRxiv 140178; doi: https://doi.org/10.1101/140178
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    In vivo phenotyping of Parkinson-specific stem cells reveals increased a-Synuclein levels but no spreading
    Kathrin Hemmer, Lisa M. Smits, Silvia Bolognin, Jens C. Schwamborn
    bioRxiv 140178; doi: https://doi.org/10.1101/140178

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