PXD070157-1

PXD070157 is an original dataset announced via ProteomeXchange.

Title	Microglial TDP-43 mediates myelin refinement and represses Tyrobp cryptic exon inclusion in mice
Description	TDP-43 proteinopathy is a hallmark of neurodegenerative disorders such as amyotrophic lateral sclerosis and frontotemporal dementia where mislocalization of TDP-43 has been observed in neurons and glial cells. However, the role of TDP-43 in microglia and the consequences of its loss-of-function remain unexplored. Combining magnetic resonance imaging, confocal, and electron microscopy we uncovered structural changes and myelin abnormalities in the early postnatal brain of mice lacking microglial TDP-43. Spatial transcriptomics further revealed an enriched interferon-response signature associated with oligodendrocyte dysfunction. Early microglial TDP-43 depletion resulted in motor deficits in adult mice. Mechanistically, knocking out TDP-43 impaired microglial ability to engulf and degrade myelin. It also led to cryptic exon inclusion in the Tyrobp mRNA, resulting in truncated DAP12 protein, thus causing defective TREM2 signaling. Our findings reveal a novel role for TDP-43 in regulating the TREM2-DAP12 axis in mice, highlighting a previously unrecognized mechanism by which TDP-43 controls microglial function.
HostingRepository	PRIDE
AnnounceDate	2026-04-29
AnnouncementXML	Submission_2026-04-29_14:47:43.896.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rosa Chiara Paolicelli
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-31 09:54:35	ID requested
⏵ 1	2026-04-29 14:47:44	announced

Dataset with its publication pending

submitter keyword: development, myelin, TDP-43,Microglia

Rosa Chiara Paoliceli
contact affiliation	UNIL | University of Lausanne Faculty of Biology and Medicine Department of Biomedical Sciences Rue du Bugnon 7 CH-1005 Lausanne
contact email	rosachiara.paolicelli@unil.ch
lab head
Rosa Chiara Paolicelli
contact affiliation	University of Lausanne, Department of Biomedical Sciences, Lausanne
contact email	rosachiara.paolicelli@unil.ch
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/2026/04/PXD070157

PRIDE project URI

• PRIDE
  1. PXD070157
     1. Label: PRIDE project
     2. Name: Microglial TDP-43 mediates myelin refinement and represses Tyrobp cryptic exon inclusion in mice