Principal Investigators

    Steven A. Goldman


    Københavns Universitet

    Contact information of lead PI



    Title of project or programme

    Modeling and correcting Huntington’s disease-associated myelin deficiency in human glial chimeras

    Source of funding information


    Total sum awarded (Euro)

    € 211,882

    Start date of award


    Total duration of award in years



    Research Abstract

    HD is characterized by neuronal degeneration but is also associated with myelin loss, potentially reflecting dysfunction of myelin-producing oligodendrocytes. We have generated oligodendrocyte progenitor cells (OPCs) from human embryonic stem cells, derived from either huntingtin (mHTT)-mutant embryos or controls, and performed RNA sequence analysis. We identified a set of key transcription factors associated with oligodendroglial differentiation and myelin biosynthesis to be significantly down-regulated in mHTT OPCs. These included MYRF, a transcription factor that coordinately activates myelin genes, which were concurrently down-regulated. We hypothesize that the hypomyelination of HD patients results from mHTT-dependent dysregulation of MYRF. We will test this hypothesis in a novel model of human glial chimeric mice, in which differentiation and myelinogenesis by OPCs may be observed and manipulated in vivo. Paired with TALEN-mediated forced expression of MYRF in HD OPCs, these experiments should provide sufficient molecular insight into the HD-dependent suppression of oligodendrocyte maturation as to potentially reverse it, thereby restoring myelinogenic competence. To that end, we will ask the following:

    Further information available at:

Types: Investments < €500k
Member States: Denmark
Diseases: N/A
Years: 2016
Database Categories: N/A
Database Tags: N/A

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