PXD025468

PXD025468 is an original dataset announced via ProteomeXchange.

Title	Altering metabolism programs cell identity via NAD+ dependent deacetylation
Description	Cells change their metabolic profiles in response to an underling gene regulatory network, but how can alterations in metabolism encode specific transcriptional instructions? Here we show that forcing metabolic change in embryonic stem cells (ESCs) promotes a developmental identity that better approximates the inner cell mass (ICM) of the mammalian blastocyst in cultures we refer to as enhanced metabolic ESCs (EMESCs). The creation of EMESCs depends on the inhibition of glycolysis and stimulation of oxidative phosphorylation (OXPHOS), that in turns activates NAD+-dependent deacetlylases of the Sirtuin family. The activation of this pathway leads to the deacetylation of histones and key transcription factors leading to a revised ICM-like gene regulatory network. The exploitation of the NAD+/NADH coenzyme normally coupled to elevated OXPHOS to program lineage specific transcription suggests new paradigms for how cells respond to alterations in their environment.
HostingRepository	PRIDE
AnnounceDate	2025-04-30
AnnouncementXML	Submission_2025-04-30_04:11:26.076.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Molly Lowndes
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue
Instrument	Orbitrap Exploris 480; Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-19 04:03:50	ID requested
⏵ 1	2025-04-30 04:11:26	announced

10.1038/s44318-025-00417-0;

Bone RA, Lowndes MP, Raineri S, R Riveiro A, Lundregan SL, Dall M, Sulek K, Romero JAH, Malzard L, Koigi S, Heckenbach IJ, Solis-Mezarino V, V, ö, lker-Albert M, Vasilopoulou CG, Meier F, Trusina A, Mann M, L Nielsen M, Treebak JT, Brickman JM, -dependent deacetylation. EMBO J, 44(11):3056-3084(2025) [pubmed]

submitter keyword: Metabolism

Transcription

NAD

Acetylation

Sirtuins

Chromatin

Enhancers

Pluripotency

Michael Lund
contact affiliation	Proteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
contact email	michael.lund.nielsen@cpr.ku.dk
lab head
Molly Lowndes
contact affiliation	Proteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
contact email	molly.lowndes@sund.ku.dk
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/2025/04/PXD025468

PRIDE project URI

• PRIDE
  1. PXD025468
     1. Label: PRIDE project
     2. Name: Altering metabolism programs cell identity via NAD+ dependent deacetylation