PXD018021

PXD018021 is an original dataset announced via ProteomeXchange.

Title	Cystatin B is essential for proliferation and interneuron migration in individuals with EPM1 epilepsy
Description	Progressive myoclonus epilepsy (PME) of Unverricht-Lundborg-type (EPM1) is an autosomal recessive neurodegenerative disorder with the highest incidence of PME worldwide. Mutations in the gene encoding cystatin B (CSTB) are the primary genetic cause of EPM1. Here, we investigate the role of CSTB during neurogenesis in vivo in the developing mouse brain and in vitro in human cerebral organoids (hCOs) derived from EPM1 patients. Remarkably, we find that CSTB (but not one of its pathological variants) is secreted into the mouse cerebral spinal fluid and the conditioned media from hCOs. In embryonic mouse brain, we find that functional CSTB influence progenitors’ proliferation and simultaneously modulate neuronal distribution by attracting interneurons to the site of secretion via cell non-autonomous mechanisms. Similarly, in patient-derived hCOs, low levels of functional CSTB result in an alteration of progenitor’s proliferation, premature differentiation, and changes in interneurons migration. Secretion and extracellular matrix organization are the biological processes particularly affected as revealed by proteomic analysis in patients’ hCOs. Overall, our data shed new light on the cellular mechanisms underlying the development of EPM1.
HostingRepository	PRIDE
AnnounceDate	2020-05-13
AnnouncementXML	Submission_2020-05-12_22:16:21.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Angela Chambery
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-12 03:59:07	ID requested
⏵ 1	2020-05-12 22:16:22	announced

Di Matteo F, Pipicelli F, Kyrousi C, Tovecci I, Penna E, Crispino M, Chambery A, Russo R, Ayo-Martin AC, Giordano M, Hoffmann A, Ciusani E, Canafoglia L, G, ö, tz M, Di Giaimo R, Cappello S, Cystatin B is essential for proliferation and interneuron migration in individuals with EPM1 epilepsy. EMBO Mol Med, 12(6):e11419(2020) [pubmed]

submitter keyword: cystatin B

human cerebral organoids

progressive myoclonus epilepsy

mass spectrometry

Angela Chambery
contact affiliation	Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", Caserta, Italy
contact email	angela.chambery@unicampania.it
lab head
Angela Chambery
contact affiliation	University of Campania "Luigi Vanvitelly"
contact email	angela.chambery@unicampania.it
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/2020/05/PXD018021

PRIDE project URI

• PRIDE
  1. PXD018021
     1. Label: PRIDE project
     2. Name: Cystatin B is essential for proliferation and interneuron migration in individuals with EPM1 epilepsy