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Cited by 186Alzheimer's disease research and treatmentsPluripotent Stem Cells ResearchNeuroinflammation and Neurodegeneration Mechanisms

Aberrant iPSC-derived human astrocytes in Alzheimer's disease

Open access
Jones, V C, Atkinson-Dell, R, Verkhratsky, A, Mohamet, L·2017·Cell Death & Disease
DOI 10.1038/cddis.2017.89PMC PMC5386580
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Abstract

The pathological potential of human astroglia in Alzheimer's disease (AD) was analysed in vitro using induced pluripotent stem cell (iPSC) technology. Here, we report development of a human iPSC-derived astrocyte model created from healthy individuals and patients with either early-onset familial AD (FAD) or the late-onset sporadic form of AD (SAD). Our chemically defined and highly efficient model provides >95% homogeneous populations of human astrocytes within 30 days of differentiation from cortical neural progenitor cells (NPCs). All astrocytes expressed functional markers including glial fibrillary acidic protein (GFAP), excitatory amino acid transporter-1 (EAAT1), S100B and glutamine synthetase (GS) comparable to that of adult astrocytes in vivo. However, induced astrocytes derived from both SAD and FAD patients exhibit a pronounced pathological phenotype, with a significantly less complex morphological appearance, overall atrophic profiles and abnormal localisation of key functional astroglial markers. Furthermore, NPCs derived from identical patients did not show any differences, therefore, validating that remodelled astroglia are not as a result of defective neural intermediates. This work not only presents a novel model to study the mechanisms of human astrocytes in vitro , but also provides an ideal platform for further interrogation of early astroglial cell autonomous events in AD and the possibility of identification of novel therapeutic targets for the treatment of AD.

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  • Four major morphological classes were identified: arborized, polarized, fibroblast-like, and rounded shapes.

    “we identified four major classes, as proposed by Jones et al. [28]: arborized, polarized, fibroblast-like and rounded shapes.”

    From Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease (2022) · cites this paper as [28]

    The Materials and methods section (Fluorescence microscopy and image analysis) explicitly says cells were classified into three categories: fibroblast-like, arborised and polarised. The Results section (Induced astrocytes from FAD and SAD patients display cellular atrophy) uses “rounded” to describe a fibroblast-like cell, not a fourth class. (LLM, conf=0.90)

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  • The continuum of GFAP/S100B-positive cells, ranging from roundish/polarized to highly arborized cells, agrees with previous studies.

    “In our study, the continuum of GFAF/S100B-positive cells, ranging from roundish/polarized ones to highly arborized cells, agrees with previous studies [27,28].”

    From Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease (2022) · cites this paper as [28]

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Research works printed but not linked: 41

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Authors
Jones, V. C., Atkinson-Dell, R., Verkhratsky, A., & Mohamet, L.
Affiliations
  • University of Lancashire (GB)
  • University of Manchester (GB)
  • Ikerbasque (ES)
Corresponding author
Mohamet, L
ORCID
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2017-03-23
Volume
8
Issue
3
Pages
e2696-e2696
ISSN
2041-4889 (ISSN-L)
DOI
10.1038/cddis.2017.89
PMC
PMC5386580
OpenAlex
W2601518322
Cited by
186
References
49
Citations by year
2026: 12 · 2025: 15 · 2024: 19 · 2023: 22 · 2022: 20 · 2021: 28 · 2020: 18 · 2019: 27 · 2018: 18 · 2017: 7
FWCI
14.17
Type
journal article
Language
en
Update notices
correction (2019-03-12)
Open access
Licence
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • CLOK (University of Central Lancashire) (acceptedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion, other-oa)
Funders
  • University of Central Lancashire
  • Wellcome Trust
  • Manchester Institute for Collaborative Research on Ageing
  • University of Manchester
  • Biotechnology and Biological Sciences Research Council
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, iPSC-derived astrocytes, early-onset familial Alzheimer's disease, astrocyte differentiation, astrocyte morphology, glial fibrillary acidic protein, glutamine synthetase, GLAST, S100B, disease models
MeSH terms
Alzheimer Disease, Astrocytes, Atrophy, Cell Differentiation, Cells, Cultured, Glial Fibrillary Acidic Protein, Glutamate-Ammonia Ligase, Humans, Male, Middle Aged, Stem Cells, Biomarkers, Up-Regulation, Excitatory Amino Acid Transporter 1, Induced Pluripotent Stem Cells, Neural Stem Cells, S100 Calcium Binding Protein beta Subunit

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