PXD004977

PXD004977 is an original dataset announced via ProteomeXchange.

Title	Enabling phenotypic drug discovery for neurological mitochondrial DNA disorders with patient-derived neural progenitor cells
Description	Mitochondrial DNA (mtDNA) mutations predominantly cause neurological diseases. Searching for therapeutic strategies is hindered by the absence of viable neural model systems due to the challenges of engineering mtDNA. We demonstrate that neural progenitor cells (NPCs), rapidly obtained from human induced pluripotent stem cells (iPSCs), retain the parental mtDNA profile and exhibit mitochondrial maturation coupled with a metabolic switch away from glycolysis. Altered calcium homeostasis and mitochondrial hyperpolarization, both potential causes of neural impairment, were observed in iPSC-derived NPCs from patients carrying a deleterious homoplasmic mutation in the mitochondrial gene MT-ATP6 (m.9185T>C). Phenotype-based high-content screenings (HCS) with FDA-approved compounds were carried out, leading to the identification of possible innovative counteracting agents. We propose iPSC-derived NPCs, displaying mild proliferative properties and proper genotype/metabotype, as a bona fide model system for the establishment of personalized phenotypic drug discovery for untreatable mtDNA disorders affecting the nervous system. Associated GEO accession number: GSE70071.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:10:34.895.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Barbara Mlody
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2016-09-15 04:36:23	ID requested
1	2017-01-31 02:28:41	announced
2	2017-02-02 03:36:53	announced	Updated project metadata.
3	2017-10-24 04:52:17	announced	Updated project metadata.
⏵ 4	2024-10-22 04:10:37	announced	2024-10-22: Updated project metadata.

10.1016/j.stem.2016.12.013;

Lorenz C, Lesimple P, Bukowiecki R, Zink A, Inak G, Mlody B, Singh M, Semtner M, Mah N, Aur, é K, Leong M, Zabiegalov O, Lyras EM, Pfiffer V, Fauler B, Eichhorst J, Wiesner B, Huebner N, Priller J, Mielke T, Meierhofer D, Izsv, á, k Z, Meier JC, Bouillaud F, Adjaye J, Schuelke M, Wanker EE, Lomb, è, s A, Prigione A, Human iPSC-Derived Neural Progenitors Are an Effective Drug Discovery Model for Neurological mtDNA Disorders. Cell Stem Cell, 20(5):659-674.e9(2017) [pubmed]

ProteomeXchange project tag: benchmarking, machine learning

curator keyword: Biomedical

submitter keyword: neural progenitors

NPCs

iPSCs

mitochondrial disorders

mtDNA mutations

MT-ATP6

Alessandro Prigione
contact affiliation	Max Delbrueck Center for Molecular Medicine (MDC), Berlin, Germany
contact email	alessandro.prigione@mdc-berlin.de
lab head
Barbara Mlody
contact affiliation	MDC
contact email	Barbara.Mlody@mdc-berlin.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/2017/01/PXD004977

PRIDE project URI

• PRIDE
  1. PXD004977
     1. Label: PRIDE project
     2. Name: Enabling phenotypic drug discovery for neurological mitochondrial DNA disorders with patient-derived neural progenitor cells