PXD066290-1

PXD066290 is an original dataset announced via ProteomeXchange.

Title	Proteostasis and Unfolded Protein Response Dynamics in a Human Neuron and Mouse Glia Co-culture Reveal a Cell-Specific Maturation Response
Description	Proteostasis, or protein homeostasis, is a tightly regulated network of cellular pathways essential for maintaining proper protein folding, trafficking, and degradation. Neurons are particularly vulnerable to proteostasis collapse due to their post-mitotic and long-lived nature and thus represent a unique cell type to understand the dynamics of proteostasis throughout development and maturation. Here, we utilized a dual-species co-culture model of human excitatory neurons and mouse glia to recapitulate and investigate cell type–specific, maturation-related changes in the proteostasis network using data-independent acquisition (DIA) LC-MS/MS proteomics. We quantified branch-specific unfolded protein response (UPR) activation by monitoring curated effector proteins downstream of the ATF6, IRE1/XBP1s, and PERK pathways, enabling a comprehensive, unbiased evaluation of UPR dynamics during in vitro neuronal maturation between 30 and 60 days. Species-specific analysis revealed that mature neurons largely preserved proteostasis, although they showed some signs of collapse, primarily in ER-to-Golgi transport mechanisms. However, these changes were accompanied by upregulation of proteostasis-related machinery and activation of the ATF6 branch, as well as maintenance of the XBP1s and PERK branches of the UPR over time. In contrast, glia exhibited broad downregulation of proteostasis factors and UPR components, independent of neuronal presence. Furthermore, we quantified stimulus-specific modulation of select UPR branches in matured neurons exposed to pharmacologic ER stressors. These findings highlight distinct, cell-type-specific stress adaptations during in vitro maturation and provide a valuable proteomic resource for dissecting proteostasis and UPR regulation in human neurons.
HostingRepository	PRIDE
AnnounceDate	2026-06-16
AnnouncementXML	Submission_2026-06-16_08:01:25.727.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD066290
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Lea Barny
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-17 17:49:58	ID requested
⏵ 1	2026-06-16 08:01:26	announced

10.1073/PNAS.2521663123;

10.6019/PXD066290;

submitter keyword: Neuronal Aging,Proteomics, Chemical Biology

Lars Plate
contact affiliation	Departments of Chemistry & Biology Vanderbilt University Associate Professor
contact email	lars.plate@vanderbilt.edu
lab head
Lea Barny
contact affiliation	Vanderbilt University
contact email	lea.a.barny@vanderbilt.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/2026/06/PXD066290

PRIDE project URI

• PRIDE
  1. PXD066290
     1. Label: PRIDE project
     2. Name: Proteostasis and Unfolded Protein Response Dynamics in a Human Neuron and Mouse Glia Co-culture Reveal a Cell-Specific Maturation Response