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Series GSE188524 Query DataSets for GSE188524
Status Public on Apr 15, 2024
Title A critical requirement for IκBα in controlling dormancy in Hematopoietic stem cells via retinoic acid during embryonic development [Cut&Tag]
Organism Mus musculus
Experiment type Other
Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
Overall design We performed cut&tag assay for H3K27me3 (IkBa Ko and WT) and Ikba with sorted embryonic fetal liver (E14.5 LT-HSCs) or AGM (E11.5 CD31+). Specifically, we generated 2 replicates from fetal liver and 2 replicates from AGM for IkBa Cut&Tag experiments. Regarding H3K27me3 experiments, replicates were only generated for E14.5 FL-HSCs and considered 3xIkBa WT and 3xIkBa KO.
Contributor(s) Thambyrajah R, Maqueda M, Fadlullah Z, Proffitt M, Hao N, Guillén Y, Casado-Pelaez M, Herrero-Molinero P, Brujas C, Castelluccio N, González J, Iglesias A, Marruecos L, Ruiz-Herguido C, Esteller M, Mereu E, Lacaud G, Espinosa L, Bigas A
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Submission date Nov 10, 2021
Last update date Apr 16, 2024
Contact name Anna Bigas
Phone +34933160440
Organization name Institut Hospital del Mar d'Investigacions Mèdiques
Department Cancer Research
Lab Stem Cells and Cancer
Street address Dr. Aiguader 88
City Barcelona
State/province Barcelona
ZIP/Postal code 08003
Country Spain
Platforms (3)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (10)
GSM5684844 E11.5_Ikba_CD31_1 [Cut&Tag]
GSM6614373 E14.5_Ikba_LT-HSC_1 [Cut&Tag]
GSM6614374 Ikba_WT_LT-HSC_H3K27me3_2 [Cut&Tag]
This SubSeries is part of SuperSeries:
GSE188525 A critical requirement for IκBα in controlling dormancy in Hematopoietic stem cells via retinoic acid during embryonic development
BioProject PRJNA779270
SRA SRP345391

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Supplementary file Size Download File type/resource
GSE188524_RAW.tar 1.2 Gb (http)(custom) TAR (of BED, BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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