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Modular neuroinflammatory network discovery from large-scale phenotypic screening in genetically heterogeneous mice [part10]

GSE294832 Mus musculus Expression profiling by high throughput sequencing 1000 samples Submitted 2026/04/11 Platform GPL24247
Summary
The central nervous system represents a uniquely immune-privileged environment, with inflammatory responses involving several resident CNS-specific cell types. While stereotyped cellular and transcriptional responses recur across varied diseases, relevant signaling pathways and regulatory networks are not fully understood. Here, we describe a screening platform based on high-throughput RNA-seq analysis and glial cell state gene set scores that enables multimodal investigation of inflammatory networks at scale. As proof-of-concept, we investigate genetically heterogeneous mice from a large-scale chemical mutagenesis screen to identify novel functionally relevant variants in six genes previously linked to human CNS disorders: Nrros, Ctsd, Smpd1, Idua, Nlrp1a, and Inpp5d . We leverage the rich and readily-interpretable data from our study to demarcate distinct inflammatory states arising from each mutation. In all, our work provides a methodology for discovering novel regulators of CNS neuroimmune homeostasis and provides a validated analysis framework for identifying discrete neuroinflammatory modules that are engaged divergently across disease contexts.
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Direct links to NCBI, no account and no request form: the whole study as GSE294832_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 1000 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1251662 and SRA study SRP579134. Searching any of these in the dataset finder brings you back here.

Study design
40 conditions, each sampled once — no replicated groups

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