| Experiment Id | GSE214699 | Name | A critical requirement for IB in controlling dormancy in Hematopoietic stem cells via retinoic acid during embryonic development [scRNA-seq_10x] |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2024-07-08 |
| 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-B. Here, we describe a dormant phenotype of LT-HSCs in the IB KO. Although IB is critical for retaining inactive NF-B 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 IB KO embryos. Furthermore, this regulation of the retinoic acid signalling by IB is further confirmed by cut and tag assay for IB 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 IB KO is evident in their dormant molecular profile. Functionally, IB KO LT-HSCs are less proliferative and respond with delayed activation upon transplantation. Overall, we identify nuclear IB as an essential player specifically for HSC specification/proliferation from the onset of HSPC emergence in the AGM. We performed 10x scRNAseq analysis in E14.5 LT-HSC fetal liver 1xWT and IB 1xKO samples. WT replicate was generated from a pool of 2 embryos and the KO replicate from a pool of 3 embryos. |
