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| Status |
Public on Jun 02, 2023 |
| Title |
Defining blood-induced microglia functions in neurodegeneration through multiomic profiling [scRNA-Seq II] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Blood protein extravasation through a disrupted blood–brain barrier and innate immune activation are hallmarks of neurological diseases and emerging therapeutic targets. However, how blood proteins polarize innate immune cells remains largely unknown. Here, we established an unbiased blood-innate immunity multiomic and genetic loss-of-function pipeline to define the transcriptome and global phosphoproteome of blood-induced innate immune polarization and its role in microglia neurotoxicity. Blood induced widespread microglial transcriptional changes, including changes involving oxidative stress and neurodegenerative genes. Comparative functional multiomics showed that blood proteins induce distinct receptor-mediated transcriptional programs in microglia and macrophages, such as redox, type 1 interferon and lymphocyte recruitment. Deletion of the blood coagulation factor fibrinogen largely reversed blood-induced microglia neurodegenerative signatures. Genetic elimination of the fibrinogen-binding motif to CD11b in Alzheimer’s disease mice reduced microglial lipid metabolism and neurodegenerative signatures that were shared with autoimmune-driven neuroinflammation in multiple sclerosis mice. Our data provide an interactive resource for investigation of the immunology of blood proteins that could support therapeutic targeting of microglia activation by immune and vascular signals.
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| Overall design |
Mouse bone-marrow derived macrophages (BMDMs) or primary mouse microglia were stimulated with fibrin, complement iC3b, LPS, or left unstimulated and then profiled with scRNA-seq.
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| Contributor(s) |
Mendiola AS, Akassoglou K |
| Citation(s) |
37291385 |
| |
| Submission date |
Apr 13, 2023 |
| Last update date |
Sep 01, 2023 |
| Contact name |
Katerina akassoglou |
| E-mail(s) |
katerina.akassoglou@gladstone.ucsf.edu
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| Organization name |
Gladstone Institutes
|
| Street address |
1650 Owens st
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| City |
San Francisco, CA |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (17)
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| This SubSeries is part of SuperSeries: |
| GSE229376 |
Defining blood-induced microglia functions in neurodegeneration through multiomic profiling |
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| Relations |
| BioProject |
PRJNA955233 |
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