PXD067561

PXD067561 is an original dataset announced via ProteomeXchange.

Title	CSF-1R regulates metal ion homeostasis in the brain – implications for neurodegenerative disease
Description	Dominant inactivating mutations in the colony stimulating factor-1 receptor (CSF1R) cause an adult-onset neurodegenerative disease associated with white matter loss and axonal degeneration designated CSF-1R related leukoencephalopathy (CRL), that is modeled in the Csf1r+/- mouse. CRL is caused by microglial dysfunction. However, the primary microglial deficit, caused by insufficient CSF-1R signaling, is unknown. To address this question, we employed single-nucleus RNA sequencing of brains from young Csf1r+/- mice without pathological or behavioral alterations. Reduction of CSF-1R signaling caused defects in mitochondrial function and metal ion homeostasis in brain macrophages, with concomitant activation of cell death and stress response pathways in oligodendrocytes and neuronal subpopulations. Reduction of metallothionein 1 (Mt1) and 3 (Mt3) gene expression was a common feature in glial and neuronal cells of Csf1r+/- mice. Overexpression of Mt1 restored metal ion homeostasis, normalized ROS production in microglia, and prevented the development of behavioral deficits, while Mt3 deletiion had disease-enhancing effects. These findings identify a novel role of the CSF-1R in the regulation of metal ion homeostasis in the brain.
HostingRepository	PRIDE
AnnounceDate	2026-02-18
AnnouncementXML	Submission_2026-02-18_12:40:16.459.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Simone Sidoli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-21 05:50:30	ID requested
⏵ 1	2026-02-18 12:40:16	announced

Dataset with its publication pending

submitter keyword: microglia dysfunction, oligodendrocyte stress, metallothionein Mt1, metal ion homeostasis, metallothionein Mt3,CSF-1R signaling, CSF1R-related leukoencephalopathy, mitochondrial dysfunction, ROS, oxidative stress, neurodegeneration, single-nucleus RNA sequencing

Simone Sidoli
contact affiliation	Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, United States
contact email	simone.sidoli@einsteinmed.edu
lab head
Simone Sidoli
contact affiliation	Albert Einstein College of Medicine
contact email	simone.sidoli@gmail.com
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/2026/02/PXD067561

PRIDE project URI

• PRIDE
  1. PXD067561
     1. Label: PRIDE project
     2. Name: CSF-1R regulates metal ion homeostasis in the brain – implications for neurodegenerative disease