PXD071015

PXD071015 is an original dataset announced via ProteomeXchange.

Title	Persulfidation alters gene regulatory programs and promotes endothelial specification
Description	Endogenously generated sulfides are conserved among species and tissues and exert multiple effects through diverse mechanisms. Although sulfides have been linked to cell fates, their role in pluripotent stem cell commitment remains unknown. Here we discovered that during directed differentiation of induced pluripotent stem cells, endogenous sulfide levels drop in all three germ layers, with the mesodermal lineage exhibiting the lowest capacity to generate these species at early specification events. Addition of a rapid releasing sulfide donor in iPSCs or mesodermal cells did not affect the redox surveillance mechanisms, however altered persulfidation and transcription of cell fate commitment pathways. In particular, sulfide supplementation in pluripotent stem cells reduced cell differentiation processes by preserving the activity of the stem cell transcription factors OCT4 and KLF4. In contrast, supplementation of sulfide during mesodermal lineage specification promoted persulfidation and activated the WNT signaling as well as enriched the activity of the ETS transcription factor family, resulting in increased transcription of angiogenic and vessel morphogenesis genes. Sulfide addition during the development of vascular organoids enhanced blood vessel morphogenesis. Taken together, these data position protein persulfidation as a timing-dependent regulator that preserves pluripotency prior to commitment but subsequently biases mesoderm toward endothelial specification, thereby emerging as a tractable redox modification for engineering stem cell fate and vascularization.
HostingRepository	PRIDE
AnnounceDate	2025-12-29
AnnouncementXML	Submission_2025-12-28_23:33:10.556.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ilka Wittig
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	biotinyl-iodoacetamidyl-3; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-20 15:49:05	ID requested
⏵ 1	2025-12-28 23:33:11	announced

10.1016/j.redox.2025.103926;

Wittig J, Xu R, Delgado Lagos F, Drekolia MK, Zhang B, Theodorou I, Chen Y, Du Y, Gupta L, Hanyu C, Yuanyuan L, Bo C, G, ü, nther S, Wittig I, Ola R, Hu J, Bibli SI, Persulfidation alters gene regulatory programs and promotes endothelial specification. Redox Biol, 89():103926(2026) [pubmed]

submitter keyword: Sulfide supplementation, endothelial commitment, persulfidation, stem cells

Janina Wittig
contact affiliation	Department of Vascular Dysfunction, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Straße 7-11, 68167 Mannheim, Germany. Department of Vascular Dysfunction, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Straße 7-11, 68167 Mannheim, Germany.
contact email	Janina.Wittig@medma.uni-heidelberg.de
lab head
Ilka Wittig
contact affiliation	Functional Proteomics, Goethe University, Frankfurt am Main , Germany
contact email	wittig@med.uni-frankfurt.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/2025/12/PXD071015

PRIDE project URI

• PRIDE
  1. PXD071015
     1. Label: PRIDE project
     2. Name: Persulfidation alters gene regulatory programs and promotes endothelial specification