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Fetal liver macrophages contribute to the hematopoietic stem cell niche by controlling granulopoiesi [bulkRNA-seq]

ABSTRACT: Investigating the effect of macrophages on the function of LT-HSC and hematopoiesis during embryogenesis in the fetal liver

ORGANISM(S): Mus musculus

PROVIDER: GSE225442 | GEO | 2023/02/17

REPOSITORIES: GEO

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Fetal liver macrophages contribute to the hematopoietic stem cell niche by controlling granulopoiesi [scRNA-seq]

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Expression data from TFIIA-non-cleavable mouse fetal liver hematopoietic stem cells

Project description:During embryogenesis, development of hematopoietic stem cells (HSC) occurs in the fetal liver and involves coordinate programs of transcription. Taspase1, a highly conserved threonine protease, directly cleaves and regulates the TFIIA families of transcription factors. We discovered that loss of Taspase1 (Tasp1-/-) or non-cleavage of TFIIAa-b (TFIIAa-b nc/nc) leads to a severe fetal liver developmental retardation that is associated with impaired HSC self-renewal and loss of HSC quiescence. We used microarray to elucidate the mechanism(s) by which TFIIA regulates fetal liver hematopoiesis, and expression of targets of HoxA9 was found to be altered by gene set enrichment analyses. Embryonic day 14.5 fetal liver HSCs (defined as Lineage-Sca-1+c-Kit+CD150+cells) of wild-type (n = 4) and TFIIAa-b nc/nc (n = 3) were analyzed.

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Fetal liver macrophages contribute to the hematopoietic stem cell niche by controlling granulopoiesi

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

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Project description:Endomucin (EMCN) currently represents the only hematopoietic stem cell (HSC) marker expressed by both murine and human HSCs. Here, we report that EMCN+ long-term repopulating HSCs (LT-HSCs; CD150+CD48−LSK) have a higher long-term multi-lineage repopulating capacity compared to EMCN− LT-HSCs. Cell cycle analyses and transcriptional profiling demonstrated that EMCN+ LT-HSCs were more quiescent compared to EMCN− LT-HSCs. Emcn−/− and Emcn+/+ mice displayed comparable steady-state hematopoiesis, as well as frequencies, transcriptional programs, and long-term multi-lineage repopulating capacity of their LT-HSCs. Complementary functional analyses further revealed increased cell cycle entry upon treatment with 5-fluorouracil and reduced granulocyte colony-stimulating factor (GCSF) mobilization of Emcn−/− LT-HSCs, demonstrating that EMCN expression by LT-HSCs associates with quiescence in response to hematopoietic stress and is indispensable for effective LT-HSC mobilization. Transplantation of wild-type bone marrow cells into Emcn−/− or Emcn+/+ recipients demonstrated that EMCN is essential for endothelial cell-dependent maintenance/self-renewal of the LT-HSC pool and sustained blood cell production post-transplant.

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