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A critical requirement for IκBα in controlling dormancy in Hematopoietic stem cells via retinoic acid during embryonic development

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE188525 | GEO | 2024/04/15

REPOSITORIES: GEO

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A critical requirement for IκBα in controlling dormancy in Hematopoietic stem cells via retinoic acid during embryonic development [Cut&Tag]

Project description:Hematopoietic Stem Cells (HSCs) originate from the E11.5 aorta-gonads-and mesonephros (AGM) region during development before they migrate to the foetal liver for proliferation and maturation, and finally seed the bone marrow around birth, their final site of residence. In the AGM, HSCs reside within Intra-aortic hematopoietic clusters (IAHC) along with hematopoietic progenitors (HPC). Molecular pathways that determine HSC fate instead of HPCs are still unknown, although inflammatory signalling has been implicated in the development of all blood cells, including NF-κB. Here, we describe a dormant phenotype of LT-HSCs in the IκBα KO. Although IκBα is critical for retaining inactive NF-κB complexes in the cytoplasm, it can regulate stem cell related genes by interacting with the PRC2 complex in the nucleus. Accordingly, we find decreased PRC2 dependent H3K27me3 accumulation at the promoters of PI3K and retinoic acid signalling molecules by cut and tag assay in AGM derived CD31+ cells, which includes HE/IAHC derived from IκBα KO embryos. Furthermore, this regulation of the retinoic acid signalling by IκBα is further confirmed by cut and tag assay for IκBα itself in CD31+ cells of the AGM and more specifically also in sorted LT-HSCs from the E14.5 foetal liver. Over-activation of the retinoic acid/PI3K levels in LT-HSCs of the IκBα KO is evident in their dormant molecular profile. Functionally, IκBα KO LT-HSCs are less proliferative and respond with delayed activation upon transplantation. Overall, we identify nuclear IκBα as an essential player specifically for HSC specification/proliferation from the onset of HSPC emergence in the AGM.

2024-04-15 | GSE188524 | GEO

A critical requirement for IκBα in controlling dormancy in Hematopoietic stem cells via retinoic acid during embryonic development [scRNA-seq_10x]

2024-04-15 | GSE214699 | GEO

A critical requirement for IκBα in controlling dormancy in Hematopoietic stem cells via retinoic acid during embryonic development [RNA-seq]

2024-04-15 | GSE188523 | GEO

Exit from HSC dormancy is controlled via vitamin A/retinoic acid

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-05-15 | GSE87814 | GEO

Exit from HSC dormancy is controlled via vitamin A/retinoic acid (II)

Project description:Identification of the role of retinoic acid on the activation of the dHSCs

2017-05-15 | GSE87807 | GEO

Exit from HSC dormancy is controlled via vitamin A/retinoic acid (I)