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

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

PROVIDER: PRJNA779270 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16902527_1.fastq.gz	Fastqsanger.gz
	SRR16902527_2.fastq.gz	Fastqsanger.gz
	SRR21788029_1.fastq.gz	Fastqsanger.gz
	SRR21788029_2.fastq.gz	Fastqsanger.gz
	SRR21788030_1.fastq.gz	Fastqsanger.gz

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

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

| PRJNA779261 | ENA

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 [RNA-seq]

2024-04-15 | GSE188523 | 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]

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

| PRJNA779271 | ENA

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

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

| PRJNA886699 | ENA

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

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

2024-04-15 | GSE188525 | GEO

Dynamic association of IκBα to chromatin during intestinal differentiation is regulated by Acetylation and N-terminal cleavage of histone H4

Project description:IκBs exert a principal function as cytoplasmic inhibitors of the NF-kB transcription factors. Additional functions for specific IκB homologues have also been described including their association to chromatin to directly regulate gene transcription. Phosphorylated and SUMOylated IκBα (pS-IκBα) specifically binds histones H2A and H4 in the stem and progenitor compartment of skin and intestine, but the mechanisms that control the recruitment of nuclear pS-IκBα to the chromatin are largely unstudied. We here show thatserine 32-36 phosphorylation of IκBα favors its binding with nucleosomes and demonstrated that p-IκBαassociation to H4 is favored by acetylation at specific H4 lysine (K) residues. Acetylated N-terminal tail of H4 is lost during intestinal cell differentiation due to histone cleavage at amino acids 17-19 by the action of trypsin or chymotrypsin, which interferes p-IκBα association to chromatin. Paradoxically, pharmacologic or genetic inhibition of trypsin and chymotrypsin activity in HT29 cells increased p-IκBα chromatin binding, associated to impaired goblet cell differentiation, which was comparable to IκBα deletion. Together our results indicate that dynamic binding of IκBα to chromatin is a requirement for intestinal cell differentiation and provide a molecular base for the restricted nuclear distribution of p-IκBα at specific stem cell compartments.

2021-06-21 | GSE167087 | GEO

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

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

| PRJNA347650 | ENA

Expression data from RH30 vector and RH30 IκBα SR cells

Project description:Classical NF-κB activity can be inhibited by overexpression of the IκBα super repressor (SR). To determine the role of NF-κB in rhabdomyosarcoma cells, we overexpressed the IκBα SR in RH30 rhabdomyosarcoma cells. IκBα SR was overexpressed in RH30 cells. RH30 vector cells were used as control group.

2018-03-30 | GSE112119 | GEO

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