Principal Investigators

    Steven A. Goldman

    Institution

    Københavns Universitet

    Contact information of lead PI

    Country

    Denmark

    Title of project or programme

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

    Source of funding information

    Lundbeckfonden

    Total sum awarded (Euro)

    € 211,882

    Start date of award

    01/03/2016

    Total duration of award in years

    3

    Keywords

    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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