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PXD021230 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDefining blood-induced microglia functions in neurodegeneration through multiomic profiling
DescriptionBlood 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.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJeffrey Johnson
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-09-01 00:27:41ID requested
12023-06-02 12:16:26announced
22023-06-09 05:21:44announced2023-06-09: Updated project metadata.
32023-11-14 09:00:56announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: neuroinflammation, itaconate, complement,Fibrinogen, macrophages, ROS, oxidative stress, microglia, transcriptomics
Contact List
Katerina Akassoglou
contact affiliationGladstone Institutes
contact emailkaterina.akassoglou@gladstone.ucsf.edu
lab head
Jeffrey Johnson
contact affiliationIcahn School of Medicine at Mount Sinai
contact emailjeffrey.johnson@mssm.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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