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  • 1.
    Lundin, Anders
    et al.
    Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden / Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Delsing, Louise
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden / Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
    Clausen, Maryam
    Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden.
    Ricchiuto, Piero
    Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden.
    Sanchez, José
    Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden.
    Sabirsh, Alan
    Pharmaceutical Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden.
    Ding, Mei
    Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden.
    Synnergren, Jane
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Zetterberg, Henrik
    Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden / Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden / Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK / UK Dementia Research Institute at UCL, London, UK.
    Brolén, Gabriella
    Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden.
    Hicks, Ryan
    Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden.
    Herland, Anna
    Department of Micro and Nanosystems KTH Royal Institute of Technology, Stockholm, Sweden / Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Falk, Anna
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Human iPS-Derived Astroglia from a Stable Neural Precursor State Show Improved Functionality Compared with Conventional Astrocytic Models2018In: Stem Cell Reports, ISSN 2213-6711, Vol. 10, no 3, p. 1030-1045Article in journal (Refereed)
    Abstract [en]

    In vivo studies of human brain cellular function face challenging ethical and practical difficulties. Animal models are typically used but display distinct cellular differences. One specific example is astrocytes, recently recognized for contribution to neurological diseases and a link to the genetic risk factor apolipoprotein E (APOE). Current astrocytic in vitro models are questioned for lack of biological characterization. Here, we report human induced pluripotent stem cell (hiPSC)-derived astroglia (NES-Astro) developed under defined conditions through long-term neuroepithelial-like stem (ltNES) cells. We characterized NES-Astro and astrocytic models from primary sources, astrocytoma (CCF-STTG1), and hiPSCs through transcriptomics, proteomics, glutamate uptake, inflammatory competence, calcium signaling response, and APOE secretion. Finally, we assess modulation of astrocyte biology using APOE-annotated compounds, confirming hits of the cholesterol biosynthesis pathway in adult and hiPSC-derived astrocytes. Our data show large diversity among astrocytic models and emphasize a cellular context when studying astrocyte biology.

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