PXD049178-1

PXD049178 is an original dataset announced via ProteomeXchange.

Title	Dysregulated Extracellular Matrix and Increased Stiffness in Lissencephaly Brain Organoid Models
Description	LIS1 mutations are known to cause lissencephaly, a neurological disorder characterized by the absence of cerebral cortical convolutions. Here we show that brain organoids with LIS1 mutations exhibit increased expression of extracellular matrix (ECM) proteins, which are less organized. The mechanical properties of the mutant organoids demonstrated increased stiffness and steady-state stiffness. These changes are associated with dysregulated mRNA and microRNA. Short-term treatment of the mutant organoids, but not the control ones, with the catalytic subunit of MMP2, which proteolytically cleaves ECM, reduced stiffness. The changes were associated with changes in water diffusion measured by MRI (Magnetic Resonance Imaging) and gene expression. We generated a model incorporating the differences in the mutant's and control brain organoid composition and organization that matches and explains our findings. Our study provides insights into the importance of the composition and organization of the ECM during human brain development and the role of LIS1 in brain structure.
HostingRepository	PRIDE
AnnounceDate	2025-03-11
AnnouncementXML	Submission_2025-03-11_01:30:16.501.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yishai Levin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-05 04:27:54	ID requested
⏵ 1	2025-03-11 01:30:16	announced

Dataset with its publication pending

submitter keyword: Extracellular Matrix, Brain, organoid

Orly Reiner
contact affiliation	Department of Molecular Genetics Weizmann Institute of Science
contact email	orly.reiner@weizmann.ac.il
lab head
Yishai Levin
contact affiliation	Weizmann Institute of Science, Israel
contact email	yishai.levin@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD049178
     1. Label: PRIDE project
     2. Name: Dysregulated Extracellular Matrix and Increased Stiffness in Lissencephaly Brain Organoid Models