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

Lundin, Anders LU ; Delsing, Louise ; Clausen, Maryam ; Ricchiuto, Piero ; Sanchez, José ; Sabirsh, Alan LU ; Ding, Mei ; Synnergren, Jane ; Zetterberg, Henrik LU and Brolén, Gabriella LU , et al. (2018) In Stem Cell Reports 10(3). p.1030-1045
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,... (More)

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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publishing date
type
Contribution to journal
publication status
published
subject
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
in
Stem Cell Reports
volume
10
issue
3
pages
16 pages
publisher
Cell Press
external identifiers
  • pmid:29456185
  • scopus:85042043028
ISSN
2213-6711
DOI
10.1016/j.stemcr.2018.01.021
language
English
LU publication?
no
id
346cf9cc-99cf-4889-b42a-750ed53820db
date added to LUP
2021-08-09 16:24:34
date last changed
2024-09-07 22:11:53
@article{346cf9cc-99cf-4889-b42a-750ed53820db,
  abstract     = {{<p>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.</p>}},
  author       = {{Lundin, Anders and Delsing, Louise and Clausen, Maryam and Ricchiuto, Piero and Sanchez, José and Sabirsh, Alan and Ding, Mei and Synnergren, Jane and Zetterberg, Henrik and Brolén, Gabriella and Hicks, Ryan and Herland, Anna and Falk, Anna}},
  issn         = {{2213-6711}},
  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}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{3}},
  pages        = {{1030--1045}},
  publisher    = {{Cell Press}},
  series       = {{Stem Cell Reports}},
  title        = {{Human iPS-Derived Astroglia from a Stable Neural Precursor State Show Improved Functionality Compared with Conventional Astrocytic Models}},
  url          = {{https://lup.lub.lu.se/search/files/101037146/Human_iPS_Derived_Astroglia.pdf}},
  doi          = {{10.1016/j.stemcr.2018.01.021}},
  volume       = {{10}},
  year         = {{2018}},
}