PXD059100

PXD059100 is an original dataset announced via ProteomeXchange.

Title	Promyelocytic leukemia protein (PML) is a regulator of eNSC differentiation, survival and mitochondrial metabolism.
Description	OThis study identifies the tumor suppressor PML as a regulator of embryonic neural stem cell (eNSC) homeostasis, highlighting its role in their proliferation, differentiation and metabolism. Loss of the promyelocytic leukemia (PML) protein has been previously linked to abnormal proliferation and diffentiation of embryonic neurons. Here we show that PML ablation inhibits the neuronal and oligodendrocytic lineages but favors the astrocytic pathway. A detailed analysis of the gene expression changes caused by PML loss in E13.5 NSC at both the RNA and protein level identifies several important cell pathways to be deregulated. Of note, PPARg activity, lipid and mitochondrial metabolism are down-regulated. Conversely, the mTOR and protein translation activities were upregulated. Pml-/- eNSC showed increased proliferation compared with the WT due to increased activation of the PI3K/AKT/mTOR pathway. In agreement with increased mTOR we detected reduced autophagic flux in Pml-/- cells and decreased proteasomal activity accompanied with an increase in the formation of intracellular aggregates. Functionally, Pml-/- mitochondria exhibit lower mitochondrial membrane potential, increased levels of ROS and morphological alterations. Mitochondrial defects observed in Pml-/- neural progenitors, might be attributed to reduced expression of PGC1a and impaired PPARγ signaling that can be transcriptionally and functionally restored by the action of a PPAR agonist. In summary, PML deficient NSC share commonalities with cells undergoing aging and/or neurodegeneration. Thus, we identify PML as a factor that supports neuronal survival and protects from neurotoxicity and propose that enforced PML expression may restore a compromised PPARg/PGC1A expression or function and offer therapeutic benefit.
HostingRepository	PRIDE
AnnounceDate	2025-09-29
AnnouncementXML	Submission_2025-09-28_17:44:30.711.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martina Samiotaki
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-20 07:32:04	ID requested
⏵ 1	2025-09-28 17:44:31	announced

Spanou S, Makatounakis T, Deligianni E, Papanikolaou S, Samiotaki M, Moretto F, Nikolaou C, Papamatheakis J, Kretsovali A, PML is crucial for neural stem cell differentiation, stress tolerance and mitochondrial integrity. Stem Cell Reports, 20(9):102598(2025) [pubmed]

10.1016/j.stemcr.2025.102598;

submitter keyword: Stem Cell, eNSC,PML

Androniki Kretsovali
contact affiliation	Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas (FORTH), 100, Plastira Str., 70013 Heraklion, Crete, Greece.
contact email	kretsova@imbb.forth.gr
lab head
Martina Samiotaki
contact affiliation	Protein Analysis Laboratory B.S.R.C. "Alexander Fleming", Alexander Fleming Street 34 16672, Vari, Greece
contact email	samiotaki@fleming.gr
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/2025/09/PXD059100

PRIDE project URI

• PRIDE
  1. PXD059100
     1. Label: PRIDE project
     2. Name: Promyelocytic leukemia protein (PML) is a regulator of eNSC differentiation, survival and mitochondrial metabolism.