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Persulfidation alters gene regulatory programs and promotes endothelial specification

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...

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Hauptverfasser: Wittig, Janina (VerfasserIn) , Xu, Ran (VerfasserIn) , Delgado Lagos, Fredy Andrés (VerfasserIn) , Drekolia, Maria-Kyriaki (VerfasserIn) , Zhang, Boran (VerfasserIn) , Theodorou, Ioannis (VerfasserIn) , Chen, Yunyun (VerfasserIn) , Du, Yali (VerfasserIn) , Gupta, Lavanya (VerfasserIn) , Hanyu, Cui (VerfasserIn) , Yuanyuan, Li (VerfasserIn) , Bo, Cheng (VerfasserIn) , Günther, Stefan (VerfasserIn) , Wittig, Ilka (VerfasserIn) , Ola, Roxana (VerfasserIn) , Hu, Jiong (VerfasserIn) , Bibli, Sofia-Iris (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: February 2026
In: Redox Biology
Year: 2026, Jahrgang: 89, Pages: 1-9
ISSN:2213-2317
DOI:10.1016/j.redox.2025.103926
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.redox.2025.103926
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2213231725004392
Volltext
Verfasserangaben:Janina Wittig, Ran Xu, Fredy Delgado Lagos, Maria-Kyriaki Drekolia, Boran Zhang, Ioannis Theodorou, Yunyun Chen, Yali Du, Lavanya Gupta, Cui Hanyu, Li Yuanyuan, Cheng Bo, Stefan Günther, Ilka Wittig, Roxana Ola, Jiong Hu, Sofia-Iris Bibli
Beschreibung
Zusammenfassung: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, it 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. 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.
Beschreibung:Online verfügbar: 28. November 2025, Artikelversion: 3. Dezember 2025
Gesehen am 10.02.2026
Beschreibung:Online Resource
ISSN:2213-2317
DOI:10.1016/j.redox.2025.103926

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