PXD033844-1

PXD033844 is an original dataset announced via ProteomeXchange.

Title	A cross-disease human microglial framework identifies disease-enriched subsets and tool compounds for microglial polarization.
Description	a. Human microglia play a pivotal role in neurological diseases, but few targeted therapies that directly modulate microglial state or function exist due to an incomplete understanding of microglial heterogeneity. We use single-cell RNA sequencing to profile live human microglia from autopsies or surgical resections across diverse neurological diseases and central nervous system regions. We observe a central divide between oxidative and heterocyclic metabolism and identify subsets associated with antigen presentation, motility, and proliferation. Specific subsets are enriched in susceptibility genes for neurodegenerative diseases or the disease-associated microglial signature. We validate subtypes in situ with an RNAscope-immunofluorescence pipeline and leverage our dataset as a classification resource, finding that iPSC model systems recapitulate substantial in vivo heterogeneity. Finally, we identify and validate candidates for chemically inducing subtype-specific states in vitro, showing that Camptothecin downregulates the transcriptional signature of disease-enriched subsets and upregulates a signature previously shown to be depleted in Alzheimer’s.
HostingRepository	PRIDE
AnnounceDate	2025-05-19
AnnouncementXML	Submission_2025-05-19_03:27:25.345.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	John Tuddenham
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Bruker Daltonics timsTOF series

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-12 04:30:15	ID requested
⏵ 1	2025-05-19 03:27:26	announced

10.1038/s41593-024-01764-7;

Tuddenham JF, Taga M, Haage V, Marshe VS, Roostaei T, White C, Lee AJ, Fujita M, Khairallah A, Zhang Y, Green G, Hyman B, Frosch M, Hopp S, Beach TG, Serrano GE, Corboy J, Habib N, Klein HU, Soni RK, Teich AF, Hickman RA, Alcalay RN, Shneider N, Schneider J, Sims PA, Bennett DA, Olah M, Menon V, De Jager PL, A cross-disease resource of living human microglia identifies disease-enriched subsets and tool compounds recapitulating microglial states. Nat Neurosci, 27(12):2521-2537(2024) [pubmed]

submitter keyword: a. microglia

single-cell RNA sequencing

neurodegeneration

neuroinflammation

disease-associated microglia

Alzheimer’s

RNAscope-immunofluorescence

microglial model systems

drug targets in neurodegeneration

Camptothecin

diaPASEF

timsTOFPro

Philip L. De Jager
contact affiliation	Center for Translational & Computational Neuroimmunology Department of Neurology 622 West 168th street New York, NY 10032
contact email	pld2115@cumc.columbia.edu
lab head
John Tuddenham
contact affiliation	Columbia University Irving Medical Center
contact email	jft2113@cumc.columbia.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/2025/05/PXD033844

PRIDE project URI

• PRIDE
  1. PXD033844
     1. Label: PRIDE project
     2. Name: A cross-disease human microglial framework identifies disease-enriched subsets and tool compounds for microglial polarization.