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Human iPS-Derived Astroglia from a Stable Neural Precursor State Show Improved Functionality Compared with Conventional Astrocytic Models
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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
Cell Press , 2018. Vol. 10, no 3, p. 1030-1045
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:kth:diva-225185DOI: 10.1016/j.stemcr.2018.01.021ISI: 000427349300028PubMedID: 29456185Scopus ID: 2-s2.0-85042043028OAI: oai:DiVA.org:kth-225185DiVA, id: diva2:1195062
Funder
Swedish Research Council, 2013-5731Swedish Foundation for Strategic Research , IB13-0074VINNOVA
Note

QC 20180404

Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-04Bibliographically approved

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