Journal article
Microglia integration into human midbrain organoids leads to increased neuronal maturation and functionality
- Abstract:
- The human brain is a complex, three-dimensional structure. To better recapitulate brain complexity, recent efforts have focused on the development of human-specific midbrain organoids. Human iPSC-derived midbrain organoids consist of differentiated and functional neurons, which contain active synapses, as well as astrocytes and oligodendrocytes. However, the absence of microglia, with their ability to remodel neuronal networks and phagocytose apoptotic cells and debris, represents a major disadvantage for the current midbrain organoid systems. Additionally, neuroinflammation-related disease modeling is not possible in the absence of microglia. So far, no studies about the effects of human iPSC-derived microglia on midbrain organoid neural cells have been published. Here we describe an approach to derive microglia from human iPSCs and integrate them into iPSC-derived midbrain organoids. Using single nuclear RNA Sequencing, we provide a detailed characterization of microglia in midbrain organoids as well as the influence of their presence on the other cells of the organoids. Furthermore, we describe the effects that microglia have on cell death and oxidative stress-related gene expression. Finally, we show that microglia in midbrain organoids affect synaptic remodeling and increase neuronal excitability. Altogether, we show a more suitable system to further investigate brain development, as well as neurodegenerative diseases and neuroinflammation.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 8.8MB, Terms of use)
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- Publisher copy:
- 10.1002/glia.24167
Authors
- Publisher:
- Wiley
- Journal:
- Glia More from this journal
- Volume:
- 70
- Issue:
- 7
- Pages:
- 1267-1288
- Publication date:
- 2022-03-09
- Acceptance date:
- 2022-02-28
- DOI:
- EISSN:
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1098-1136
- ISSN:
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0894-1491
- Pmid:
-
35262217
- Language:
-
English
- Keywords:
- Pubs id:
-
1243499
- Local pid:
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pubs:1243499
- Deposit date:
-
2022-04-11
- ARK identifier:
Terms of use
- Copyright holder:
- Sabate-Soler et al.
- Copyright date:
- 2022
- Rights statement:
- © 2022 The Authors. GLIA published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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