PXD075039

PXD075039 is an original dataset announced via ProteomeXchange.

Title	Multimodal Proteomics reveals dysregulated secretion and ECM remodeling in schizophrenia patient iPSC-derived astrocytes
Description	Astrocytes are increasingly implicated in the pathophysiology of schizophrenia (SCZ), yet how astrocytic dysfunction contributes to disease-relevant neuronal abnormalities remains unclear. Here, we use mass spectrometry–based proteomics to profile lysates (proteome) and secreted (secretome) proteins from iPSC-derived astrocytes originating from 9 SCZ patients and 8 healthy controls. Compartment-specific analyses showed that lysates were enriched for mitochondrial and nuclear pathways, whereas astrocyte-conditioned media (ACM) was enriched for extracellular matrix (ECM) and vesicle-associated proteins. Differential expression analysis revealed minimal overlap between dysregulated proteins in lysates and ACM, indicating modality-specific effects of SCZ genetic background. Interestingly, ECM proteins and key secreted cues involved in synaptic development, including MFGE8, SEMA3C, were selectively reduced in SCZ ACM, whereas RNA-processing proteins were aberrantly increased. This is in line with previously reported microRNA enrichment in extracellular vesicles (EV) derived from SCZ patients. Gene set analyses further identified altered secretion-related pathways, nuclear processes, and potential involvement of autophagy-dependent release mechanisms. Together, these findings demonstrate astrocytic protein homeostasis and extracellular signaling aberrations in SCZ iPSCs, providing mechanistic insight into astrocyte-mediated contributions to synaptic and circuit deficits in the disorder.
HostingRepository	PRIDE
AnnounceDate	2026-06-29
AnnouncementXML	Submission_2026-06-28_16:26:14.588.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Frank Koopmans
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	L-cysteine methyl disulfide; monohydroxylated residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-28 00:21:56	ID requested
⏵ 1	2026-06-28 16:26:15	announced

Li WP, Laupman KE, Beekhuis-Hoekstra SD, Thanou E, Klaassen RV, Sullivan PF, Posthuma D, Smit AB, Koopmans F, Heine VM, Multimodal Proteomics Reveals Dysregulated Secretion and ECM Remodelling in Schizophrenia Patient iPSC-Derived Astrocytes. Cells, 15(12):(2026) [pubmed]

10.3390/cells15121052;

submitter keyword: astrocytes, proteomics, iPSC,Schizophrenia, protein secretion

August B. Smit
contact affiliation	Dept. of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
contact email	guus.smit@vu.nl
lab head
Frank Koopmans
contact affiliation	Vrije Universiteit Amsterdam
contact email	frank.koopmans@vu.nl
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/PXD075039

PRIDE project URI

• PRIDE
  1. PXD075039
     1. Label: PRIDE project
     2. Name: Multimodal Proteomics reveals dysregulated secretion and ECM remodeling in schizophrenia patient iPSC-derived astrocytes