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Human iPS-Derived Astroglia from a Stable Neural Precursor State Show Improved Functionality Compared with Conventional Astrocytic Models
Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden / Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
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. (Bioinformatik, Bioinformatics)ORCID iD: 0000-0003-2899-3801
Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden.
Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden.
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2018 (English)In: Stem Cell Reports, ISSN 2213-6711, Vol. 10, no 3, p. 1030-1045Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
2018. Vol. 10, no 3, p. 1030-1045
Keywords [en]
apolipoproteins E, astrocytes, calcium signaling, cell differentiation, drug discovery, glutamate plasma membrane transport proteins, high-throughput screening assays, induced pluripotent stem cells, neurodegenerative diseases, neuroinflammation
National Category
Cell Biology
Research subject
Bioinformatics
Identifiers
URN: urn:nbn:se:his:diva-14757DOI: 10.1016/j.stemcr.2018.01.021ISI: 000427349300028PubMedID: 29456185Scopus ID: 2-s2.0-85042043028OAI: oai:DiVA.org:his-14757DiVA, id: diva2:1184286
Available from: 2018-02-20 Created: 2018-02-20 Last updated: 2018-04-18Bibliographically approved

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Delsing, LouiseSynnergren, Jane

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