Asset Details
Do you wish to reserve the book?
IκBα controls dormancy in hematopoietic stem cells via retinoic acid during embryonic development
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
IκBα controls dormancy in hematopoietic stem cells via retinoic acid during embryonic development
Do you wish to request the book?
IκBα controls dormancy in hematopoietic stem cells via retinoic acid during embryonic development
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
IκBα controls dormancy in hematopoietic stem cells via retinoic acid during embryonic development
2024
Overview
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.
Hematopoietic stem cells are generated during development, though how and when they become dormant long term-HSCs remains unclear. Here they show that retinoic acid receptor levels are regulated by a IκBα-PRC2 axis in HSCs, and that
IκBα
KO mice have HSCs that are fewer in number, but functionally and molecularly more dormant.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/51
/ 38/15
/ 38/39
/ 38/77
/ 38/88
/ 64/60
/ Acids
/ Animals
/ Aorta
/ Dormancy
/ Embryonic Development - genetics
/ Female
/ Gene Expression Regulation, Developmental
/ Hematopoietic Stem Cells - cytology
/ Hematopoietic Stem Cells - metabolism
/ Humanities and Social Sciences
/ Mice
/ NF-KappaB Inhibitor alpha - genetics
/ NF-KappaB Inhibitor alpha - metabolism
/ Polycomb Repressive Complex 2 - genetics
/ Polycomb Repressive Complex 2 - metabolism
/ Science
