PXD019112

PXD019112 is an original dataset announced via ProteomeXchange.

Title	Defective metabolic programming impairs early neuronal morphogenesis in neural cultures and an organoid model of Leigh syndrome
Description	Leigh syndrome (LS) is a severe manifestation of mitochondrial disease in children and is currently incurable. The lack of effective models hampers our understanding of the mechanisms underlying the neuronal pathology of LS. Using patient-derived induced pluripotent stem cells and CRISPR/Cas9 engineering, we developed a human model of LS due to mutations in the complex IV assembly gene SURF1. Single-cell RNA-sequencing and multi-omics analysis revealed compromised neuronal morphogenesis in mutant neural cultures and brain organoids. The defects emerged at the level of neural progenitor cells (NPCs), which retained a glycolytic proliferative state that failed to instruct neuronal morphogenesis. LS NPCs carrying mutations in the complex I gene NDUFS4 recapitulated morphogenesis defects. Interventions supporting the metabolic programming of NPCs restored neuronal morphogenesis, including SURF1 gene augmentation and PGC1A induction via bezafibrate treatment. Our findings provide mechanistic insights and suggest interventional strategies for a rare mitochondrial disease with major unmet medical needs.
HostingRepository	PRIDE
AnnounceDate	2021-01-29
AnnouncementXML	Submission_2021-01-29_04:58:56.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Meierhofer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-12 01:37:38	ID requested
⏵ 1	2021-01-29 04:58:56	announced

Dataset with its publication pending

submitter keyword: mitochondrial disease

Leigh syndrome

iPSCs

NPCs

brain organoids

SURF1

Prof. Dr. Alessandro Prigione
contact affiliation	Principal Investigator „Stem Cell Metabolism“ Group Department of General Pediatrics, Neonatology, and Pediatric Cardiology University Clinic Düsseldorf (UKD), Heinrich Heine University (HHU) Moorenstraße 5, 40225 Düsseldorf, Germany Building 13.41, Level 3, Room 29
contact email	Alessandro.Prigione@med.uni-duesseldorf.de
lab head
David Meierhofer
contact affiliation	Mass Spectrometry Facility MPIMG
contact email	meierhof@molgen.mpg.de
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/2021/01/PXD019112

PRIDE project URI

• PRIDE
  1. PXD019112
     1. Label: PRIDE project
     2. Name: Defective metabolic programming impairs early neuronal morphogenesis in neural cultures and an organoid model of Leigh syndrome