2f317de5-46b4-44b5-ad78-9be30a8aef08 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001007760 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:This dataset contains bam files mapped to hg19 (exome and panel) or hg38 (RNA) that either were primary bone marrow cells or sorted human cells after long term engraftment in NSG mice treated with LOXL inhibitor
| EGAD00001008695 | EGA
Project description:Pluripotent stem cells (PSC) represent an alternative source of hematopoietic stem cells (HSCs). Clinical translation is impeded by limited engraftment of human (h)PSC-multipotent progenitor cells (MPP). This barrier suggests that additional cues are required for definitive hematopoiesis. We hypothesized that vascular niche producing Notch ligands Jagged-1 (JAG1) and Delta-like ligand-4 (DLL4) would drive definitive hematopoiesis. To test our hypothesis, hes2 human embryonic stem cells (hESC) 2 and Macaca nemestrina (Mn) iPSC line-7 were differentiated with cytokines ± endothelial cells (EC), which express JAG1 and DLL4. EC co-culture supported emergence of 8-fold more CD34+CD45+ cells compared to co-culture with cytokines ± ECs with JAG1 or DLL4 knockdown. EC-induced cells exhibit Notch activation and express HSC-specific targets of Notch signaling RUNX1 and GATA2. EC-induced PSC-MPP engraft at a higher level in NSG mice compared to cytokine-induced cells (10% >5 months), and selection increased engraftment (30%). Long-term engraftment and the myeloid-to-lymphoid ratio achieved with vascular niche induction is similar to levels achieved for cord blood MPP and up to 20-fold higher than hPSC-MPP engraftment. Our findings identify a previously underappreciated role for endothelial Notch ligands in PSC definitive hematopoiesis and production of long-term engrafting CD34+ cells and suggest they are critical for HSC emergence. Transcriptome sequencing of Macaca nemestrina (Mn) iPSCs
2015-12-31 | E-GEOD-64644 | biostudies-arrayexpress
Project description:Corticotrophin-releasing hormone (CRH) is a key regulator involved in the stress pathway, yet its functions in the direct regulation of human stem/ progenitor cells (HSPCs) are poorly understood. Here we report that human CD34+ HSPCs constitutively expressed CRH receptor1. Treatment with CRH increased the motility and deformability of human HSPCs. Intravital two-photon imaging of bone tissues showed that CRH stimulated migration and bone marrow homing of HSPCs in vivo. Pretreatment of human HSPCs promoted homing and long-term engraftment when transplanted into primary and secondary NSG mice. Mechanistically, CRH modulates cell mechanics by extracellular matrix (ECM) remodeling, correlating with increased expression of the ECM protein THBS2 and activities of the Rho family small GTPases. Collectively, these findings show that CRH, a neurotransmitter, regulates biomechanics, which is correlated with its new functions in HSPSs migration, homing and engraftment, designating CRH as a promising drug candidate to facilitate clinical HSC transplantation.
2023-09-01 | GSE240116 | GEO
Project description:Ppm1d T/+ mice exhibit altered BM composition. The aim is to determine the molecular mechanisms possibly responsible for this alterations in sorted long-term hematopoietic stem cells isolated from bone marrow. Long-term HSCs (LT-HSCs sorted from 12-week-old WT and Ppm1DT/+ mice. The Ppm1dT/+ HSC transcriptome shows enrichment of MYC, mTOR compared to WT.
2023-12-31 | E-MTAB-13090 | biostudies-arrayexpress
Project description:Stromal Repair via Long-term Engraftment of Primary Bone Marrow Stroma Improves Hematopoietic Stem Cell Transplantation
2017-07-02 | GSE79091 | GEO
Project description:<p>We are studying the natural history, pathogenesis and treatment of patients with WHIM syndrome, an immunodeficiency disorder characterized by warts, hypogammaglobulinemia, recurrent infections and neutropenia usually due to autosomal dominant gain-of-function mutations in chemokine receptor <i>CXCR4</i>. We have identified a patient born with WHIM syndrome and the WHIM mutation <i>CXCR4<sup>R334X</sup></i> who has been disease-free for 20 years and who lacks <i>CXCR4<sup>R334X</sup></i> in myeloid cells, the cells that drive disease manifestations. She is a genetic and hematopoietic mosaic, since she still has the mutation in lymphoid cells and non-hematopoietic cells. Cytogenetics and microarray analysis revealed that the mechanism of loss of the mutation was deletion of the mutant allele from one copy of chromosome 2. Whole genome sequencing of patient neutrophil and skin fibroblast genomic DNA revealed that the mechanism of deletion was chromothripsis, a process of chromosome shattering resulting in deletions and rearrangements of the non-deleted chromosomal segments. In the patient, this process evidently occurred in a single hematopoietic stem cell (HSC), resulting in deletion of the disease allele <i>CXCR4<sup>R334X</sup></i> and one copy of 163 other genes on chromosome 2. This HSC evidently acquired a growth advantage and repopulated the HSC population and the myeloid lineage. Consistent with this, studies using gene targeted mice in competitive bone marrow transplantation experiments revealed that selective <i>Cxcr4</i> haploinsufficiency (inactivation of one copy of <i>Cxcr4</i> and not of any other genes) was sufficient to confer a strong engraftment advantage over bone marrow cells from wild type mice as well as bone marrow cells from a mouse model of WHIM syndrome. These results suggest that <i>CXCR4</i> knockdown may be a useful strategy to enhance bone marrow engraftment in the absence of toxic bone marrow conditioning regimens.</p>
| phs000856 | dbGaP
Project description:OCI-AML3, a human acute myeloid leukemia cell line, was inoculated into NOD/SCID/IL-2rγnull (NSG) mice. After engraftment and leukemic expansion were documented, mice were divided into 3 groups: control, or treatment for 24 or 72 hours with daily injections of LY2510294, a CXCR4-inhibitory peptide. OCI-AML3 cells were isolated from peripheral blood (PB), bone marrow (BM), or spleen (SP) for gene expression profiling (GEP).
2015-06-03 | GSE64623 | GEO
Project description:Pluripotent stem cells (PSC) represent an alternative source of hematopoietic stem cells (HSCs). Clinical translation is impeded by limited engraftment of human (h)PSC-multipotent progenitor cells (MPP). This barrier suggests that additional cues are required for definitive hematopoiesis. We hypothesized that vascular niche producing Notch ligands Jagged-1 (JAG1) and Delta-like ligand-4 (DLL4) would drive definitive hematopoiesis. To test our hypothesis, hes2 human embryonic stem cells (hESC) 2 and Macaca nemestrina (Mn) iPSC line-7 were differentiated with cytokines ± endothelial cells (EC), which express JAG1 and DLL4. EC co-culture supported emergence of 8-fold more CD34+CD45+ cells compared to co-culture with cytokines ± ECs with JAG1 or DLL4 knockdown. EC-induced cells exhibit Notch activation and express HSC-specific targets of Notch signaling RUNX1 and GATA2. EC-induced PSC-MPP engraft at a higher level in NSG mice compared to cytokine-induced cells (10% >5 months), and selection increased engraftment (30%). Long-term engraftment and the myeloid-to-lymphoid ratio achieved with vascular niche induction is similar to levels achieved for cord blood MPP and up to 20-fold higher than hPSC-MPP engraftment. Our findings identify a previously underappreciated role for endothelial Notch ligands in PSC definitive hematopoiesis and production of long-term engrafting CD34+ cells and suggest they are critical for HSC emergence.
2015-12-31 | GSE64644 | GEO
Project description:Long-term engraftment of engineered human plasma cells
| PRJNA873089 | ENA
Project description:The identification of small molecules which either increase the number and/or enhance the activity of CD34+ hematopoietic stem and progenitor cells (HSPCs) during ex-vivo expansion has remained challenging. Applying an unbiased in vivo chemical screen in a transgenic (c-myb:EGFP) zebrafish embryo model, histone deacetylase inhibitors (HDACI) (valproic acid, resminostat and entinostat) were shown to significantly amplify the number of phenotypic hematopoietic precursors. The identified HDACIs were confirmed to significantly enhance also the expansion of human HSPCs during ex vivo treatment. Long-term functionality of ex vivo expanded human HSPCs was verified in a xenotransplantation model using NSG mice. However, the HDACI induced proliferation of HSPCs was associated with short-term functional changes. One of the identified hits, valproic acid (VPA), increased the adhesion capacity of CD34+ cells on primary mesenchymal stromal cells and reduced their chemokine-mediated migration capacity in vitro. In line with the reduced migratory potential in vitro, homing as well as early engraftment of VPA treated human CD34+ cells was significantly impaired in the xenotransplantation model. Our data confirms that HDACI treatment leads to a net expansion of HSPCs cells with long-term engraftment potential across different species. However impaired homing and short-term-engraftment has to be kept in mind when designing clinical transplantation protocols. In addition, our gene expression analysis (RNA-Seq) revealed expression of several genes that were altered in CD34+ cells by VPA treatment including cell adhesion molecules and Notch and wnt genes which has been shown to be involved in preservation of stem cell properties.
2017-11-01 | GSE90552 | GEO