Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA171826 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The importance of extrinsic regulation of hematopoietic stem cell activity is increasingly acknowledged. Here we report the generation of a new niche system, which supports expansion of mouse hematopoietic stem cells in vitro. Characterization of this niche revealed a transcriptional regulatory network including four critical factors, namely FOS, SPI1, KLF10 and TFEC. Interestingly, these factors are essential for osteoclastogenesis, thus revealing an osteoclastic network that supports hematopoietic stem cell self-renewal. Lentiviral vectors containing putative transcription factors regulating HSC expansion were transfected into GPE cells and gene expression values were compared to empty vector controls.
2013-12-31 | E-GEOD-39835 | biostudies-arrayexpress
Project description:The importance of extrinsic regulation of hematopoietic stem cell activity is increasingly acknowledged. Here we report the generation of a new niche system, which supports expansion of mouse hematopoietic stem cells in vitro. Characterization of this niche revealed a transcriptional regulatory network including four critical factors, namely FOS, SPI1, KLF10 and TFEC. Interestingly, these factors are essential for osteoclastogenesis, thus revealing an osteoclastic network that supports hematopoietic stem cell self-renewal.
2013-12-31 | GSE39835 | GEO
Project description:Maintenance of hematopoietic stem cell (HSC) function in the niche is an orchestrated event. Osteomacs (OM), are key cellular components of the niche. Previously, we documented that osteoblasts, OM, and megakaryocytes interact to promote hematopoiesis. Here, we further characterize OM and identify megakaryocyte-induced mediators that augment the role of OM in the niche. Single cell mRNAseq, mass spectrometry, and CyTOF examination of megakaryocyte-stimulated OM suggested that upregulation of CD166 and Embigin on OM augment their hematopoiesis maintenance function. CD166 knockout OM or shRNA-Embigin knockdown OM, confirmed that loss of these molecules significantly reduced OM ability to augment the osteoblast-mediated hematopoietic enhancing activity. Recombinant CD166 and Embigin partially substituted for OM function, characterizing both proteins as critical mediators of OM hematopoietic function. Our data identify Embigin and CD166 as OM-regulated critical components of HSC function in the niche and potential participants in various in vitro manipulations of stem cells.
2024-01-11 | MSV000093840 | MassIVE
Project description:During embryonic development the placental vasculature acts as a major hematopoietic niche, where endolthelial to hematopoietic transition ensures emergence of hematopoietic stem cells (HSCs). However, the molecular mechanisms that regulate the placental hematoendothelial niche are poorly understood. Using a parietal trophoblast giant cell (TGC)-specific knockout mouse model and single-cell RNA-sequencing, we show that the paracrine factors secreted by this single layer of TGCs are critical in the development of this niche. Disruptions in the TGC specific paracrine signaling leads to the loss of HSC population and the concomitant expansion of a KDR+/DLL4+/PROM1+ hematoendothelial cell-population in the placenta. Combining single-cell transcriptomics and receptor-ligand pair analyses, we also define the parietal TGC-dependent paracrine signaling network and identify Integrin signaling as a fundamental regulator of this process. Our study elucidates novel mechanisms by which non autonomous signaling from the primary parietal TGCs maintains the delicate placental hematopoietic-angiogenic balance and ensures embryonic and extraembryonic development.
2023-06-25 | GSE163286 | GEO
Project description:Jak3 is the only non-promiscuous member of the Jak family of secondary messengers. Jak3–/– mice display defective T and NK cell development, which results in a SCID phenotype. As a result, studies to date have focused on understanding and targeting the cell-autonomous role of Jak3 in immunity, while functional Jak3 expression outside the hematopoietic system remains largely unreported. We show that Jak3 is expressed in endothelial cells across hematopoietic and non-hematopoietic organs, with heightened expression in the bone marrow. The bone marrow niche is understood as a network of different cell types that regulate hematopoietic function. We show that the Jak3–/– bone marrow niche is deleterious for the maintenance of long-term repopulating hematopoietic stem cells (LT-HSCs) and that JAK3-overexpressing endothelial cells have increased potential to expand LT-HSCs in vitro. Increased arterial zonation in the bone marrow of Jak3–/– mice further situates Jak3 as a marker of sinusoidal endothelium. This work may serve to identify a novel function for a highly specific tyrosine kinase in the bone marrow vascular niche and to further characterize the LT-HSC function of sinusoidal endothelium.
2021-10-20 | GSE159755 | GEO
Project description:Hematopoietic stem cell transplantation (HSCT) represents the most effective therapeutic approach for hematopoietic malignancies, bone marrow (BM) failure syndromes, and primary immunodeficiency diseases. However, the clinical demand for HSCT is constrained by current limitations in HSC sources and expansion technologies. The BM niche is crucial providing a supportive microenvironment for the self-renewal and differentiation of HSCs, and its rejuvenation is essential for rapid and effective hematopoietic recovery. In this study, we demonstrate that costal-cartilage-derived stem cells (CDSCs) can achieve hematopoietic reconstruction comparable to HSCT, even with a significantly reduced number of hematopoietic stem and progenitor cells (HSPCs), while exhibiting low chimerism. We further show that transplanted CDSCs differentiate into various cell types, including bone marrow stromal cells (BMSCs), endothelial cells, and osteoblasts, and secrete pro-hematopoietic factors that restore the damaged BM niche. Moreover, in vitro-expanded CDSCs exhibit elevated expression of BMSC markers and enhance hematopoietic recovery in injury models. Notably, the combination of CDSCs with cyclosporine A is effective in treating aplastic anemia in mouse models. Collectively, these findings propose a novel strategy for treating BM hematopoietic failure through microenvironmental restoration and broaden the potential therapeutic scope of HSCT.
2025-02-13 | GSE289080 | GEO
Project description:Hematopoietic stem cell transplantation (HSCT) represents the most effective therapeutic approach for hematopoietic malignancies, bone marrow (BM) failure syndromes, and primary immunodeficiency diseases. However, the clinical demand for HSCT is constrained by current limitations in HSC sources and expansion technologies. The BM niche is crucial providing a supportive microenvironment for the self-renewal and differentiation of HSCs, and its rejuvenation is essential for rapid and effective hematopoietic recovery. In this study, we demonstrate that costal-cartilage-derived stem cells (CDSCs) can achieve hematopoietic reconstruction comparable to HSCT, even with a significantly reduced number of hematopoietic stem and progenitor cells (HSPCs), while exhibiting low chimerism. We further show that transplanted CDSCs differentiate into various cell types, including bone marrow stromal cells (BMSCs), endothelial cells, and osteoblasts, and secrete pro-hematopoietic factors that restore the damaged BM niche. Moreover, in vitro-expanded CDSCs exhibit elevated expression of BMSC markers and enhance hematopoietic recovery in injury models. Notably, the combination of CDSCs with cyclosporine A is effective in treating aplastic anemia in mouse models. Collectively, these findings propose a novel strategy for treating BM hematopoietic failure through microenvironmental restoration and broaden the potential therapeutic scope of HSCT.
2025-02-14 | GSE289526 | GEO
Project description:Crosstalk between mesenchymal stromal cells (MSCs) and hematopoietic stem and cells (HSCs) is essential for hematopoietic homeostasis and lineage output. Ebf1-deficient MSCs have reduced mesenchymal lineage potential. Ebf1 deletion in Cxcl12-abundant reticular (CAR) cells and PDGFRα+Sca1+CD45-CD31-Lin- (PαS) cells in the bone marrow decreased the numbers of HSPCs and myeloid cells. EBF1 in the bone marrow niche regulates a transcriptional program that determines the functional interactions with HSCs and the long-term balance between the myeloid and lymphoid cell fates.
2020-03-01 | GSE127970 | GEO
Project description:Isolation and functional characterization of the arteriole hematopoietic stem cell niche
| PRJNA261726 | ENA
Project description:A transcriptome study in mouse hematopoietic stem cells was performed using a sensitive SAGE method, in an attempt to detect medium and low abundant transcripts expressed in these cells. Among a total of 31,380 unique transcript, 17,326 (55%) known genes were detected, 14,054 (45%) low-copy transcripts that have no matches to currently known genes. 3,899 (23%) were alternatively spliced transcripts of the known genes and 3,754 (22%) represent anti-sense transcripts from known genes.
2009-05-20 | GSE16139 | GEO