PXD021230-3

PXD021230 is an original dataset announced via ProteomeXchange.

Title	Defining blood-induced microglia functions in neurodegeneration through multiomic profiling
Description	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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:00:56.087.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeffrey Johnson
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-01 00:27:41	ID requested
1	2023-06-02 12:16:26	announced
2	2023-06-09 05:21:44	announced	2023-06-09: Updated project metadata.
⏵ 3	2023-11-14 09:00:56	announced	2023-11-14: Updated project metadata.
4	2024-10-22 05:46:25	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: neuroinflammation, itaconate, complement,Fibrinogen, macrophages, ROS, oxidative stress, microglia, transcriptomics

Katerina Akassoglou
contact affiliation	Gladstone Institutes
contact email	katerina.akassoglou@gladstone.ucsf.edu
lab head
Jeffrey Johnson
contact affiliation	Icahn School of Medicine at Mount Sinai
contact email	jeffrey.johnson@mssm.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/06/PXD021230

PRIDE project URI

• PRIDE
  1. PXD021230
     1. Label: PRIDE project
     2. Name: Defining blood-induced microglia functions in neurodegeneration through multiomic profiling