| First Author | Thambyrajah R | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 4673 |
| PubMed ID | 38824124 | Mgi Jnum | J:349013 |
| Mgi Id | MGI:7646440 | Doi | 10.1038/s41467-024-48854-5 |
| Citation | Thambyrajah R, et al. (2024) IkappaBalpha controls dormancy in hematopoietic stem cells via retinoic acid during embryonic development. Nat Commun 15(1):4673 |
| abstractText | 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 IkappaBalpha (Nfkbia, the inhibitor of NF-kappaB) as a critical regulator of HSC proliferation throughout development. IkappaBalpha balances retinoic acid signaling levels together with the epigenetic silencer, PRC2, specifically in HSCs. Loss of IkappaBalpha decreases proliferation of HSC and induces a dormancy related gene expression signature instead. Also, IkappaBalpha 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 IkappaBalpha deficient HSCs. Overall, we show that the proliferation index in the developing HSCs is regulated by a IkappaBalpha-PRC2 axis, which controls retinoic acid signaling. |
