Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA307693 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The low homing and engraftment efficiency especially in context of low availability of donor CD34+ HSPCs is a major challenge, which limits the clinical applications of HSC therapies. SDF-1/CXCR4 axis plays a principle role in the homing and engraftment of hematopoietic stem/progenitor cells. Activation of CXCR4 induces cell trafficking and homing to the marrow microenvironment, where it retains hematopoietic stem cells in close contact with marrow stromal cells. The aim of our study is to understand the mechanisms of other molecules acting along with CXCR4 to provide new insights in the regulation of cell phenotypes. This data shows the transcriptional profiling of human hematopoetic leukemic k562 cells comparing control, wild type and two different mutant cells where mutant cells have constitutively activated CXCR4 gene expression where mutant 1 and 2 have different aminoacid substituions. biological replicates: three control, three wild type, three mutant 1, three mutant 2
2016-02-29 | E-GEOD-76544 | biostudies-arrayexpress
Project description:The low homing and engraftment efficiency especially in context of low availability of donor CD34+ HSPCs is a major challenge, which limits the clinical applications of HSC therapies. SDF-1/CXCR4 axis plays a principle role in the homing and engraftment of hematopoietic stem/progenitor cells. Activation of CXCR4 induces cell trafficking and homing to the marrow microenvironment, where it retains hematopoietic stem cells in close contact with marrow stromal cells. The aim of our study is to understand the mechanisms of other molecules acting along with CXCR4 to provide new insights in the regulation of cell phenotypes. This data shows the transcriptional profiling of human hematopoetic leukemic k562 cells comparing control, wild type and two different mutant cells where mutant cells have constitutively activated CXCR4 gene expression where mutant 1 and 2 have different aminoacid substituions.
2016-02-29 | GSE76544 | 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:<p>Acute myeloid leukemia is an aggressive clonal malignancy of the bone marrow that is the direct result of sequential acquisition of mutations in a single lineage of cells. In this study, we investigate a model in which this mutational acquisition occurs serially in long-lived self-renewing hematopoietic stem cells eventually resulting in frank acute myeloid leukemia. Coding mutations in multiple AML patients were identified using exome sequencing followed by sanger sequencing validation. The level of these mutations was then assessed in residual hematopoietic stem cells from each patient using targeted deep sequencing. These population-level estimates of mutant allele burden were then validated in single cell assays targeted to the identified mutations. This allowed for determination of the order of acquisition of the mutations that preceded the development of the leukemia. The results of this study identify pre-leukemic hematopoietic stem cell clones that could contribute to patient relapse and outcome.</p>
| phs000549 | dbGaP
Project description:Homeobox genes encode transcription factors that control patterning of virtually all organ systems including the hematopoietic system. However, the role of homeobox genes in controlling development of the erythroid and megakaryocytic lineages is poorly understood. In this study, we investigated the role of the homeobox gene DLX4 in erythroid and megakaryocytic differentiation using the bipotent cell line K562 as a model. We compared the global gene expression profile of K562 cells that stably overexpressed DLX4 with that of vector-control K562 cells. As positive controls, global gene expression profiles were evaluated in vector-control K562 cells that were stimulated with Activin A (ActA) to induce erythroid differentiation and in vector-control K562 cells that were stimulated with phorbol 12-myristate 13-acetate (PMA) to induce megakaryocytic differentiation. Our study provides insights into the role of homeobox genes in controlling differentiation of the erythroid and megakaryocytic lineages. Three groups of samples were included: DLX4 vs Empty vector; Activin A vs None; PMA vs DMSO
2015-09-02 | E-GEOD-63888 | biostudies-arrayexpress
Project description:HSPC harbor constitutively active antiviral blocks that can be induced by type I IFN in certain cell types such as THP-1 cells but not in the K562 cell line. In the effort to identify such factors we compared trascriptomes from HSPC, THP1 and K562 stimulated or not with type I IFN
2023-03-05 | E-MTAB-6598 | biostudies-arrayexpress
Project description:To investigate the effect of STAT3 activation on the expression of gastric cancer cells, expression profile was compared in MKN28 cells overexpressed with control vector vs mouse constitutively activated STAT3 mutant (STAT3c).
2016-02-27 | GSE78714 | GEO
Project description:Fusion protein AML1-ETO resulted from t(8;21) translocation is highly related to leukemia development. We have previously shown that the expression of AE9a, a spliced form of AML1-ETO, can rapidly cause leukemia in mouse. To understand how AML1-ETO is involved in leukemia development, we used AE9a leukemia model to identify a novel AE9a interacting proteins PRMT1 (protein arginine methyltransferase 1) from primary leukemic cells expressing AE9a. To examine whether PRMT1 is involved in AE9a-mediated transcription regulation, genome wide gene expression analysis is carried out in hematopoietic cell line K562 (wild type or AE9a expressing) treated with (-) control siRNA or siPRMT1. Wild type or AE9a-expressing K562 cells with control siRNA or siPRMT1 in triplicate
2012-06-17 | E-GEOD-28135 | biostudies-arrayexpress
Project description:Transcriptional profiling of cytokines and its receptors in primary murine lymphoblastoid cells (pML cells), which are lymphomatous cells from HTLV-1 TAX transgenic mice. ATL is a T-cell malignancy caused by HTLV-I, and presents as an aggressive leukemia with characteristic widespread leukemic cell infiltration into visceral organs and skin. The molecular mechanisms associated with leukemic cell infiltration are poorly understood. We have employed mouse models of ATL to investigate the role of chemokines in this process. Transfer of splenic lymphomatous cells from transgenic to SCID mice rapidly reproduces a leukemia and lymphoma which is histologically identical to human disease. It could be shown that lymphomatous cells exhibit specific chemotactic activity in response to SDF-1α. Lymphomatous cells exhibited surface expression of CXCR4, the specific receptor of SDF-1α and chemotaxis was associated with down regulation of CXCR4 expression and phosphorylation of intracellular ERK1/2. AMD3100, a CXCR4 antagonist, was found to inhibit both SDF-1α - induced migration and phosphorylation of ERK1/2. Investigation of cultured cells from human ATL patients revealed identical findings. Employing the SCID mouse model it could be demonstrated that AMD3100 inhibited infiltration of lymphomatous cells into liver and lung tissues in vivo. These results demonstrate the involvement of the SDF-1α /CXCR4 interaction as one mechanism of leukemic cell migration and this may provide a novel target as part of combination therapy for ATL. pML cells vs. pan T cells from C57BL6 mice.
2010-05-15 | E-GEOD-17341 | biostudies-arrayexpress
Project description:Co-IP/MS of HA-Gli2 (P1-6A), the constitutively active mutant of Gli2 in NIH/3T3 Flp-in cells. The cells were either ciliated or depleted of cilia by expression of the dominant negative mutant of Kif3a (dnKif3a). Sample 8033:A is ciliated cells, sample 8033:B is unciliated cells.
2023-12-30 | MSV000093739 | MassIVE