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Chi3l3 induces oligodendrogenesis in an experimental model of autoimmune neuroinflammation

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  • Sarah C. Starossom

    (Charité – Universitätsmedizin Berlin
    Max Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin Berlin
    Charité - Universitätsmedizin Berlin
    Brigham and Women’s Hospital, Harvard Medical School)

  • Juliana Campo Garcia

    (Charité – Universitätsmedizin Berlin)

  • Tim Woelfle

    (Charité – Universitätsmedizin Berlin)

  • Silvina Romero-Suarez

    (Charité – Universitätsmedizin Berlin)

  • Marta Olah

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Fumihiro Watanabe

    (Laboratory of Neural Stem Cells and Functional Neurogenetics, Department of Neurology-The Ohio State University Wexner Medical Center)

  • Li Cao

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Ada Yeste

    (Brigham and Women’s Hospital, Harvard Medical School)

  • John J. Tukker

    (Charité – Universitätsmedizin Berlin
    Charité – Universitätsmedizin Berlin)

  • Francisco J. Quintana

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Jaime Imitola

    (Brigham and Women’s Hospital, Harvard Medical School
    Laboratory of Neural Stem Cells and Functional Neurogenetics, Department of Neurology-The Ohio State University Wexner Medical Center)

  • Franziska Witzel

    (Computational Modeling in Medicine, Charité– Universitätsmedizin Berlin)

  • Dietmar Schmitz

    (Charité - Universitätsmedizin Berlin
    Charité – Universitätsmedizin Berlin
    Computational Modeling in Medicine, Charité– Universitätsmedizin Berlin)

  • Markus Morkel

    (Charité – Universitätsmedizin Berlin)

  • Friedemann Paul

    (Max Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin Berlin
    Charité - Universitätsmedizin Berlin
    Charité - Universitätsmedizin Berlin)

  • Carmen Infante-Duarte

    (Charité – Universitätsmedizin Berlin)

  • Samia J. Khoury

    (Brigham and Women’s Hospital, Harvard Medical School
    American University of Beirut Medical Center)

Abstract

In demyelinating diseases including multiple sclerosis (MS), neural stem cells (NSCs) can replace damaged oligodendrocytes if the local microenvironment supports the required differentiation process. Although chitinase-like proteins (CLPs) form part of this microenvironment, their function in this differentiation process is unknown. Here, we demonstrate that murine Chitinase 3-like-3 (Chi3l3/Ym1), human Chi3L1 and Chit1 induce oligodendrogenesis. In mice, Chi3l3 is highly expressed in the subventricular zone, a stem cell niche of the adult brain, and in inflammatory brain lesions during experimental autoimmune encephalomyelitis (EAE). We find that silencing Chi3l3 increases severity of EAE. We present evidence that in NSCs Chi3l3 activates the epidermal growth factor receptor (EGFR), thereby inducing Pyk2-and Erk1/2- dependent expression of a pro-oligodendrogenic transcription factor signature. Our results implicate CLP-EGFR-Pyk2-MEK-ERK as a key intrinsic pathway controlling oligodendrogenesis.

Suggested Citation

  • Sarah C. Starossom & Juliana Campo Garcia & Tim Woelfle & Silvina Romero-Suarez & Marta Olah & Fumihiro Watanabe & Li Cao & Ada Yeste & John J. Tukker & Francisco J. Quintana & Jaime Imitola & Franzis, 2019. "Chi3l3 induces oligodendrogenesis in an experimental model of autoimmune neuroinflammation," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08140-7
    DOI: 10.1038/s41467-018-08140-7
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