IκBα controls dormancy in hematopoietic stem cells via retinoic acid during embryonic development

Recent findings suggest that Hematopoietic Stem Cells (HSC) and progenitors arise simultaneously and independently of each other already in the embryonic aorta-gonad mesonephros region, but it is still unknown how their different features are established. Here, we uncover IκBα (Nfkbia, the inhibitor...

Descripción completa

Detalles Bibliográficos
Autores: Thambyrajah, Roshana, Maqueda, Maria, Fadlullah, Zaki, Proffitt, Martin, Neo, Wen Hao, Guillén, Yolanda, Casado-Peláez, Marta, Herrero-Molinero, Patricia, Brujas, Carla, Castelluccio, Noemi, González, Jessica, Iglesias, Arnau, Marruecos, Laura, Ruiz-Herguido, Cristina, Esteller, Manel, Mereu, Elisabetta, Lacaud, Georges, Espinosa Blay, Lluís, Bigas Salvans, Anna
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/70856
Acceso en línea:http://hdl.handle.net/10230/70856
http://dx.doi.org/10.1038/s41467-024-48854-5
Access Level:acceso abierto
Palabra clave:Haematopoiesis
Haematopoietic stem cells
Histone post-translational modifications
Descripción
Sumario:Recent findings suggest that Hematopoietic Stem Cells (HSC) and progenitors arise simultaneously and independently of each other already in the embryonic aorta-gonad mesonephros region, but it is still unknown how their different features are established. Here, we uncover IκBα (Nfkbia, the inhibitor of NF-κB) as a critical regulator of HSC proliferation throughout development. IκBα balances retinoic acid signaling levels together with the epigenetic silencer, PRC2, specifically in HSCs. Loss of IκBα decreases proliferation of HSC and induces a dormancy related gene expression signature instead. Also, IκBα deficient HSCs respond with superior activation to in vitro culture and in serial transplantation. At the molecular level, chromatin regions harboring binding motifs for retinoic acid signaling are hypo-methylated for the PRC2 dependent H3K27me3 mark in IκBα deficient HSCs. Overall, we show that the proliferation index in the developing HSCs is regulated by a IκBα-PRC2 axis, which controls retinoic acid signaling.

Similares en LA Referencia