Gata2_chipseq
Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR895375.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description:The transcription factor (TF) GATA2, is crucial for the formation, and lifelong homeostasis of hematopoietic stem cells. Mono-Allelic germline disruptions of GATA2, result in haploinsufficiency syndromes. These disorders display variable manifestations, including immune deficiency, lymphedema, pulmonary proteinosis, and bone marrow failure. The later is presented by myelodysplastic changes (MDS), that subsequently evolve to leukemia (AML). MDS/AML are the most devastating, yet most consistent outcomes, designating GATA2 deficiency as one major predisposing condition to AML development.
2023-09-15 | GSE143308 | GEO
Project description:Transcriptional enhancer elements are responsible for orchestrating the temporal and spatial control over gene expression that is crucial for programming cell identity during development. Here, we describe a novel enhancer element important for regulating Prox1 expression in lymphatic endothelial cells. This evolutionarily conserved enhancer is bound by key lymphatic transcriptional regulators including GATA2, FOXC2, NFATC1 and PROX1. CRISPR-Cas9 genome editing of this enhancer element revealed that deletion of only 5 nucleotides encompassing the GATA2 binding site has a dramatic impact on lymphatic vascular development; mice homozygous for this deletion die soon after birth exhibiting profound lymphatic vascular defects. Lymphatic endothelial cells in enhancer mutant mice exhibit reduced levels of genes characteristic of lymphatic endothelial cell identity and acquire characteristics of hemogenic endothelium, including the capacity to generate hematopoietic cells. These data reveal the first transcriptional enhancer element important for regulating Prox1 expression and lymphatic endothelial cell identity and suggest that Prox1 is important for repressing hemogenic cell identity in the lymphatic endothelium.
2022-11-21 | GSE129633 | GEO
Project description:Transcriptional enhancer elements are responsible for orchestrating the temporal and spatial control over gene expression that is crucial for programming cell identity during development. Here, we describe a novel enhancer element important for regulating Prox1 expression in lymphatic endothelial cells. This evolutionarily conserved enhancer is bound by key lymphatic transcriptional regulators including GATA2, FOXC2, NFATC1 and PROX1. CRISPR-Cas9 genome editing of this enhancer element revealed that deletion of only 5 nucleotides encompassing the GATA2 binding site has a dramatic impact on lymphatic vascular development; mice homozygous for this deletion die soon after birth exhibiting profound lymphatic vascular defects. Lymphatic endothelial cells in enhancer mutant mice exhibit reduced levels of genes characteristic of lymphatic endothelial cell identity and acquire characteristics of hemogenic endothelium, including the capacity to generate hematopoietic cells. These data reveal the first transcriptional enhancer element important for regulating Prox1 expression and lymphatic endothelial cell identity and suggest that Prox1 is important for repressing hemogenic cell identity in the lymphatic endothelium.
2022-11-21 | GSE129632 | GEO
Project description:The transcription factor (TF) GATA2, is crucial for the formation, and lifelong homeostasis of hematopoietic stem cells. Mono-Allelic germline disruptions of GATA2, result in haploinsufficiency syndromes. These disorders display variable manifestations, including immune deficiency, lymphedema, pulmonary proteinosis, and bone marrow failure. The later is presented by myelodysplastic changes (MDS), that subsequently evolve to leukemia (AML). MDS/AML are the most devastating, yet most consistent outcomes, designating GATA2 deficiency as one major predisposing condition to AML development. To date, biomolecular trajectories of GATA2 deficiency, just vaguely delineated explanatory mechanisms. Experimental models recapitulating the disease evolution are meager, and functional studies are thus hampered. Here, we created murine models, reflecting the evolution of GATA2 deficiency, from gestational stage, to malignancy. We imposed the oncogenic driving force of TF ERG, upon Gata2 heterozygote and WT mice, to create a credible model. Both ERG/Gata2WT, and ERG/Gata2het mice developed leukemia, yet ERG/Gata2het, sustained an accelerated disease, resulting in diminished survival (p<0.0001). Subsequently, we obtained expression profiles of pre-leukemic blood precursors, using high throughput genomics, followed by functional assessments of self-renewal and cycling capacities. These studies elucidated a unique proliferative phenotype held by ERG/Gata2het progenitors. Additional expression analyses, metabolic assays, and electrons-microscopy inspections, suggested ERG/Gata2het progenitors uniquely relay on oxidative phosphorylation, and harbor alterations in mitochondrial structure and function. Excitingly, similar expression signature and morphological features were observed in human GATA2+/R396W cells, and in profiles of Inv(3)/GATA2MUT AML’s. We here provide new insights into GATA2 deficiency evolutionary course, underscoring the need to deconvolute pre-malignant stages in translational studies.
2022-07-01 | GSE143238 | GEO
Project description:Angiopoietin-Tie1 signaling is required for lymphatic vascular integrity and both ANGPT2 and TIE1 genetic variants have been associated with lymphedema in patients1, 2. Concurrent with growth-factor signaling, mechanical forces sensed by lymphatic endothelial cells (LECs) are also needed to regulate lymphatics3, 4. How these two pathways might interact in the lymphatic system is unknown. Here, we identified a regulatory network in LECs linking activation of the mechanosensory channel, PIEZO1 to Angiopoietin-Tie signaling and repression of a downstream FOXO1 transcriptional response. RNAseq analysis of dermal LECs from Tie1-deficient embryos showed persistent FOXO1 activity with downregulation of LEC-associated genes including Ccl21a, Foxc2, Gata2 and Gja4, as well as increased expression of the mechanosensory channel, Piezo1. Activation of PIEZO1 in human dermal LECs (HDLECs) by the small molecule agonist, Yoda1, triggered exocytosis of the Tie ligand, Angiopoietin-2 (ANGPT2), activation of Tie/AKT/PI3K signaling and export of FOXO1 out of the nucleus. Our data identify a novel molecular pathway linking mechano-transduction to ANGPT2-Tie1 activity and dynamic modulation of FOXO1 activity needed for patterning and function of the lymphatic system
2024-03-05 | GSE211849 | GEO
Project description:The lymphatic system removes fluid from the interstitial space and returns it to the blood with a tremendous capacity: during inflammation, lymph flow rates can increase dramatically; however, during chronic lymphedema, there is little or no flow. The ability of lymphatic endothelium to sense and actively regulate this function is unknown, and shear stress is likely a key indicator of lymph flow. We profiled gene expression in human dermal microvascular lymphatic endothelial cells exposed to 0, 2 and 20 dyn/cm2 shear stress as representative of chronic lymphedema, normal, and acute inflammatory conditions, respectively. We found important adaptive responses correlated to multiple aspects of lymphatic function. Importantly, shear stress upregulated intracellular water and solute transporters while decreasing cell-cell adhesion and basement membrane components and increasing cell-matrix interactions. This data indicate that during high loading conditions, both passive and active drainage function increases, while conversely when fluid drainage is blocked, transport function is diminished in the lymphatic endothelium. These data demonstrate the first functional-adaptive response of lymphatic endothelium to flow conditions, thus indicating that the lymphatic endothelium plays an active role in regulating their function. Keywords: Shear stress, dose response, cell type comparison
2009-12-01 | GSE8852 | GEO
Project description:The lymphatic system removes fluid from the interstitial space and returns it to the blood with a tremendous capacity: during inflammation, lymph flow rates can increase dramatically; however, during chronic lymphedema, there is little or no flow. The ability of lymphatic endothelium to sense and actively regulate this function is unknown, and shear stress is likely a key indicator of lymph flow. We profiled gene expression in human dermal microvascular lymphatic endothelial cells exposed to 0, 2 and 20 dyn/cm2 shear stress as representative of chronic lymphedema, normal, and acute inflammatory conditions, respectively. We found important adaptive responses correlated to multiple aspects of lymphatic function. Importantly, shear stress upregulated intracellular water and solute transporters while decreasing cell-cell adhesion and basement membrane components and increasing cell-matrix interactions. This data indicate that during high loading conditions, both passive and active drainage function increases, while conversely when fluid drainage is blocked, transport function is diminished in the lymphatic endothelium. These data demonstrate the first functional-adaptive response of lymphatic endothelium to flow conditions, thus indicating that the lymphatic endothelium plays an active role in regulating their function. Keywords: Shear stress, dose response, cell type comparison Lymphatic endothelial cells were subjected to 0, 2, or 20 dyn/cm2 shear stress; blood endothelial cells were subjected to 0 or 20 dyn/cm2 shear stress. Four samples were used for each cell type/shear level group for a total of 20 samples. Each sample was independently compared to human universal reference RNA via two-color microarray analysis for a total of 20 arrays. In all cases, the experimental samples were labeled with Cy5 dye while the reference RNA was labeled with Cy3.
2009-11-30 | E-GEOD-8852 | biostudies-arrayexpress
Project description:The lymphatic vascular system plays important roles in the maintenance of interstitial fluid pressure, the afferent immune response and the absorption of dietary lipids. However, the molecular mechanisms that control lymphatic vessel network maturation and function remain largely unknown. To identify novel players in lymphatic vessel function, we isolated pure populations of lymphatic and blood vascular endothelial cells from mouse intestine using fluorescence-activated high-speed cell sorting and performed transcriptional profiling. We found that the axonal guidance molecules semaphorin 3A (Sema3A) and Sema3D were specifically expressed by lymphatic vessels. Quantitative PCR of ex vivo isolated cells and immunohistochemical analysis confirmed these results. Importantly, we found that the semaphorin receptor neuropilin-1 (Nrp-1) is expressed on the valves of collecting lymphatic vessels. Treatment of mice in utero (E12.5-E16.5) with an antibody that blocks Sema3A binding to Nrp-1, but not with an antibody that blocks VEGFA binding to Nrp-1, resulted in abnormal development of collecting lymphatic vessels and valves, and aberrant smooth muscle cell coverage. Conversely, Sema3A-deficient mice displayed branching defects of collecting lymphatic vessels as well as impaired valve development. Together, these results reveal an unanticipated role of Sema3A/Nrp-1 signaling in the maturation of the lymphatic vascular network. Colon single-cell suspensions were prepared by a fast protocol that minimizes the RNA degradation. Fluorescence-activated cell sorting (FACS) was used to sort blood vascular endothelial cells (BEC) and lymphatic endothelial cells (LEC). 4 animal-matched pairs of LEC and BEC were chosen based on the quality of extracted and amplified material to provide homogenous groups of biological replicates. This gave 8 samples to analyze. Samples present LEC and BEC isolated from 4 healthy normal mice. The 4 mice used present the 4 biological replicates.
2012-06-15 | E-GEOD-22034 | biostudies-arrayexpress
Project description:Mouse surgical model of acute lymphedema induction. We performed three sets of microarrays with three replicates each for a total of 9 arrays. Each array was run using pooled RNA from three animals. The three conditions were Normal tail skin (no intervention), Lymphedema tail skin(due to surgical lymphatic vessel blockage), and Surgical Sham control tail skin(surgical incision with no lymphatic vessel blockage). 15ug of test and reference (e17.5 mouse whole embryo) RNA was used for labeling. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set
2006-03-04 | GSE4333 | GEO
Project description:The lymphatic vascular system maintains tissue fluid homeostasis, helps mediate afferent immune responses and promotes cancer metastasis. MicroRNAs (miRNAs) have recently emerged as key and potent regulators of the genome that control virtually all aspects of cell and organism biology. Surprisingly, the physiological importance and functional activities of miRNAs in the lymphatic vascular system have not been explored. To address this, we first defined the in vitro miRNA expression profiles of primary human lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BVECs). Comparative analysis of these profiles identified 4 BVEC-signature and 2 LEC-signature miRNAs. Further expression analysis by quantitative real-time PCR analysis and by in situ hybridization (ISH) studies confirmed these vascular lineage-specific expression patterns in vivo. Functional characterization of the BVEC-signature miRNA, miR-31, identified a novel BVEC-specific post-transcriptional regulatory mechanism that inhibits lymphatic-specific transcription programs in vitro and lymphatic vascular development during Xenopus embryogenesis. These effects are, in part, mediated via direct post-transcriptional repression of PROX1, a master regulator of lymphatic lineage-specific differentiation. Together, these findings indicate that miR-31, and miRNAs in general, are potent regulators of vascular lineage-specific differentiation and development.
2010-06-04 | GSE16908 | GEO