@article{10902/37500,
year = {2024},
url = {https://hdl.handle.net/10902/37500},
abstract = {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 IkBalfa (Nfkbia, the inhibitor of NF-?B) as a critical regulator of HSC proliferation throughout development. IkBalfa balances retinoic acid signaling levels together with the epigenetic silencer, PRC2, specifically in HSCs. Loss of IkBalfa decreases proliferation of HSC and induces a dormancy related gene expression signature instead. Also, IkBalfa 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 IkBalfa deficient HSCs. Overall, we show that the proliferation index in the developing HSCs is regulated by a IkBalfa-PRC2 axis, which controls retinoic acid signaling.},
organization = {This work was funded by grants from SAF2016-75613-R, PID2019-
104695RB-I00, and PDC2021-120817-I00 from Agencia Estatal de
Investigación (AEI) and SLT002/16/00299 from Department of Health,
Generalitat de Catalunya. The work in G.L. laboratory is supported by
Blood Cancer UK (19014) and Cancer Research UK Manchester Institute
Core Grant (C5759/A27412). R.T. is a recipient of BP2016(00021) and BP/
MSCA 2018(00034) fellowship programs from Generalitat de Catalunya/MSCA. M.M. is a recipient of a grant from the Instituto Carlos III,
grant number CA22/00011 (co-funded by the European Social Fund
Plus, ESF+, and by the European Union)},
publisher = {Nature Publishing Group},
publisher = {Nature Communications, 2024, 15(1), 4673},
title = {IkBalfa controls dormancy induction in Hematopoietic stem cell development via retinoic acid},
author = {Thambyrajah, Roshana and Maqueda, Maria and Fadlullah, Muhammad Zaki and Proffitt, Martin and Neo, Wen Hao and Guillén, Yolanda and Casado Pelaez, Marta and Herrero Molinero, Patricia and Brujas, Carla and Castelluccio, Noemi and González, Jessica and Iglesias, Arnau and Marruecos, Laura and Ruiz Herguido, Cristina and Esteller, Manel and Mereu, Elisabetta and Lacaud, Georges and Espinosa, Lluis and Bigas, Anna},
}