Academic Journal
IκBα controls dormancy in hematopoietic stem cells via retinoic acid during embryonic development
| العنوان: | IκBα controls dormancy in hematopoietic stem cells via retinoic acid during embryonic development |
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| المؤلفون: | Roshana Thambyrajah, Maria Maqueda, Muhammad Zaki Fadlullah, Martin Proffitt, Wen Hao Neo, Yolanda Guillén, Marta Casado-Pelaez, Patricia Herrero-Molinero, Carla Brujas, Noemi Castelluccio, Jessica González, Arnau Iglesias, Laura Marruecos, Cristina Ruiz-Herguido, Manel Esteller, Elisabetta Mereu, Georges Lacaud, Lluis Espinosa, Anna Bigas |
| المصدر: | Nature Communications, Vol 15, Iss 1, Pp 1-17 (2024) |
| بيانات النشر: | Nature Portfolio |
| سنة النشر: | 2024 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Science |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2041-1723 |
| Relation: | https://doi.org/10.1038/s41467-024-48854-5; https://doaj.org/toc/2041-1723; https://doaj.org/article/e2c4801c11ca4edbbdc98a6129f4d110 |
| DOI: | 10.1038/s41467-024-48854-5 |
| الاتاحة: | https://doi.org/10.1038/s41467-024-48854-5 https://doaj.org/article/e2c4801c11ca4edbbdc98a6129f4d110 |
| رقم الانضمام: | edsbas.4D3B858E |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20411723 |
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| DOI: | 10.1038/s41467-024-48854-5 |