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Single-cell transcriptomics defines an improved, validated monoculture protocol for differentiation of human iPSC to microglia

Abstract:
There is increasing genetic evidence for the role of microglia in neurodegenerative diseases, including Alzheimer's, Parkinson's, and motor neuron disease. Therefore, there is a need to generate authentic in vitro models to study human microglial physiology. Various methods have been developed using human induced Pluripotent Stem Cells (iPSC) to generate microglia, however, systematic approaches to identify which media components are actually essential for functional microglia are mostly lacking. Here, we systematically assess medium components, coatings, and growth factors required for iPSC differentiation to microglia. Using single-cell RNA sequencing, qPCR, and functional assays, with validation across two labs, we have identified several medium components from previous protocols that are redundant and do not contribute to microglial identity. We provide an optimised, defined medium which produces both transcriptionally and functionally relevant microglia for modelling microglial physiology in neuroinflammation and for drug discovery.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41598-022-23477-2

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Pathology Dunn School
Role:
Author


Publisher:
Springer Nature
Journal:
Scientific Reports More from this journal
Volume:
12
Article number:
19454
Publication date:
2022-11-14
Acceptance date:
2022-11-01
DOI:
EISSN:
2045-2322
Pmid:
36376339


Language:
English
Keywords:
Pubs id:
1305071
Local pid:
pubs:1305071
Deposit date:
2022-11-22

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