Human iPS-Derived Astroglia from a Stable Neural Precursor State Show Improved Functionality Compared with Conventional Astrocytic Models

Anders Lundin, Louise Delsing, Maryam Clausen, Piero Ricchiuto, José Sanchez, Alan Sabirsh, Mei Ding, Jane Synnergren, Henrik Zetterberg, Gabriella Brolén, Ryan Hicks, Anna Herland, Anna Falk

Research output: Contribution to journalArticlepeer-review

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Abstract

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.

Original languageEnglish
Pages (from-to)1030-1045
Number of pages16
JournalStem Cell Reports
Volume10
Issue number3
DOIs
Publication statusPublished - 2018 Mar 13
Externally publishedYes

Subject classification (UKÄ)

  • Neurosciences
  • Cell and Molecular Biology
  • Cell Biology

Free keywords

  • Apolipoproteins E/metabolism
  • Astrocytes/metabolism
  • Brain/metabolism
  • Cell Differentiation/physiology
  • Cells, Cultured
  • Humans
  • Induced Pluripotent Stem Cells/metabolism
  • Neural Stem Cells/metabolism
  • Neurons/metabolism

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