GEO series
Immune response to adeno-associated viral vectors in a human iPSC-derived microglia chimeric mouse model
GSE312740
Homo sapiens; Mus musculus
Expression profiling by high throughput sequencing
16 samples
Submitted 2026/03/25
Platform GPL24676Platform GPL24247
Summary
Adeno-associated virus (AAV)-based gene therapy for severe neurological diseases is challenged by immune responses, which are difficult to study accurately in genetically divergent rodent models or in in vitro human iPSC-derived microglia (iMGL) that acquire activated phenotypes lacking complex brain environment cues. To address this, we generated human microglia chimeric mice. We developed a high-yield iMGL differentiation protocol incorporating a cryopreservation stopping point at the induced hematopoietic precursor cell (iHPC) stage, which increased flexibility and enabled high level of chimerism. Engrafted iMGL transcriptionally and phenotypically resembled primary human microglia and were functionally active, displaying phagocytosis and immune response to inflammatory stimuli. Assessment of AAV serotypes revealed that murine microglia induced a larger immune response compared to human iMGL, cautioning against overinterpreting inflammatory responses in rodent models. This model provides a critical tool to define the human immune response to AAVs early in vector discovery.
Published in
Detrez JR, Eykens C, Gillet G et al.
· Cell reports methods 2026
· PMID 41895259
· doi:10.1016/j.crmeth.2026.101362
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE312740_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 16 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1375804 and SRA study SRP651849. Searching any of these in the dataset finder brings you back here.
Study design
16 conditions, each sampled once — no replicated groups
Read from 16 sample titles: 16 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9352241 S1 25DIV iPSC-Derived Microglia
- GSM9352242 S2 NSG-CSF1 With Inhibitors
- GSM9352243 S3 NSG-CSF1 Without Inhibitors
- GSM9352244 S4 NSG-CSF1 Without Inhibitors
- GSM9352245 S5 NSG-CSF1 Without Inhibitors
- GSM9352246 1A NSG-CSF1 With iMGL engrafted
- GSM9352247 1B NSG-CSF1 Without iMGL engrafted
- GSM9352248 1C NSG-CSF1 With iMGL engrafted
- GSM9352249 1D NSG-CSF1 With iMGL engrafted
- GSM9352250 1E NSG-CSF1 Without iMGL engrafted
- GSM9352251 1F NSG-CSF1 Without iMGL engrafted
- GSM9352252 2G NSG-CSF1 Without iMGL engrafted
- GSM9352253 2H NSG-CSF1 Without iMGL engrafted
- GSM9352254 2I NSG-CSF1 Without iMGL engrafted
- GSM9352255 2J NSG-CSF1 With iMGL engrafted
- GSM9352256 2K NSG-CSF1 With iMGL engrafted
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