Depletion of CHD4 sensitizes AML cells but not normal CD34+ progenitors to genotoxic agents by relaxing chromatin and impairing DSB repair.
Depletion of the chromatin remodeler CHD4 sensitizes AML blasts to genotoxic agents and reduces tumor formation.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Nijmegen Breakage Syndrome fibroblasts and iPSCs: cellular models for uncovering disease-associated signaling pathways and establishing a screening platform for anti-oxidants.
Specimen part, Disease, Disease stage, Cell line
View SamplesNijmegen Breakage Syndrome (NBS) is a rare autosomal recessive genetic disorder, first described 1981 in Nijmegen, Holland. The characteristics of NBS include genomic instability (resulting in early onset of malignancies), premature aging, microcephaly and other growth retardations, immune deficiency, and impaired puberty and fertility in females. The consequence of these manifestations is a severe decrease in average life span, caused by cancer or infection of the respiratory and urinary tract. We reprogrammed fibroblasts from NBS patients into induced pluripotent stem cells (iPSCS) to bypass premature senescence and to generate an unlimited cell source for modeling purposes. We screened the influence of antioxidants on intracellular levels of ROS and DNA damage and found that EDHB was able to decrease DNA damage in the presence of high oxidative stress. Furthermore, we found that NBS fibroblasts, but not NBS-iPSCs were more susceptible to the induction of DNA damage than their normal counterparts. We performed global transcriptome analysis comparing NBS to normal fibroblasts and NBS-iPSCs to hESCs. There, we found, that TP53 was activated and cell cycle genes broadly down-regulated in NBS fibroblasts and up-regulation of glycolysis specifically in NBS-iPSCs.
Nijmegen Breakage Syndrome fibroblasts and iPSCs: cellular models for uncovering disease-associated signaling pathways and establishing a screening platform for anti-oxidants.
Specimen part, Disease, Disease stage, Cell line
View SamplesNijmegen Breakage Syndrome (NBS) is a rare autosomal recessive genetic disorder, first described 1981 in Nijmegen, Holland. The characteristics of NBS include genomic instability (resulting in early onset of malignancies), premature aging, microcephaly and other growth retardations, immune deficiency, and impaired puberty and fertility in females. The consequence of these manifestations is a severe decrease in average life span, caused by cancer or infection of the respiratory and urinary tract. We reprogrammed fibroblasts from NBS patients into induced pluripotent stem cells (iPSCS) to bypass premature senescence and to generate an unlimited cell source for modeling purposes. We screened the influence of antioxidants on intracellular levels of ROS and DNA damage and found that EDHB was able to decrease DNA damage in the presence of high oxidative stress. Furthermore, we found that NBS fibroblasts, but not NBS-iPSCs were more susceptible to the induction of DNA damage than their normal counterparts. We performed global transcriptome analysis comparing NBS to normal fibroblasts and NBS-iPSCs to hESCs. There, we found, that TP53 was activated and cell cycle genes broadly down-regulated in NBS fibroblasts and up-regulation of glycolysis specifically in NBS-iPSCs.
Nijmegen Breakage Syndrome fibroblasts and iPSCs: cellular models for uncovering disease-associated signaling pathways and establishing a screening platform for anti-oxidants.
Specimen part, Disease, Disease stage
View SamplesMillions of patients suffer from lymphedema worldwide. Supporting the contractility of lymphatic collectors is an attractive target for pharmacological therapy of lymphedema. However, lymphatics have mostly been studied in animals, while the cellular and molecular characteristics of human lymphatic collectors are largely unknown. We studied epifascial lymphatic collectors of the thigh, which were isolated for autologous transplantations. Our immunohistological studies identify additional markers for LECs (vimentin, CCBE-1). We show and confirm differences between initial and collecting lymphatics concerning the markers ESAM1, D2-40 and LYVE-1. Our transmission electron microscopic studies reveal two types of smooth muscle cells (SMCs) in the media of the collectors with dark and light cytoplasm. We observed vasa vasorum in the media of the largest collectors, as well as interstitial Cajal-like cells, which are highly ramified cells with long processes, caveolae, and lacking a basal lamina. They are in close contact with SMCs, which possess multiple caveolae at the contact sites. Immunohistologically we identified such cells with antibodies against vimentin and PDGFRa, but not CD34 and cKIT. With Next Generation Sequencing we searched for highly expressed genes in the media of lymphatic collectors, and found therapeutic targets, suitable for acceleration of lymphatic contractility, such as neuropeptide Y receptors 1, and 5; tachykinin receptors 1, and 2; purinergic receptors P2RX1, and 6, P2RY12, 13, and 14; 5-hydroxytryptamine receptors HTR2B, and 3C; and adrenoceptors a2A,B,C. Our studies represent the first comprehensive characterization of human epifascial lymphatic collectors, as a prerequisite for diagnosis and therapy. Overall design: The transcriptome of 6 different normal human lymphatic collectors (Lyko1, Lyko 4-12, Lyko 5, Lyko12, Lyko13, Lyko26) from the dermis of the thigh of women between 44 and 61 years of age was compared to cultures of human dermal lymphatic endothelial cells (LEC1, LEC2, HD-LEC9A) and a mixture of 3 different human dermal blood endothelial cells (HD-BEC-CA) to identify potential drug targets in the media of the collectors.
Morphological and Molecular Characterization of Human Dermal Lymphatic Collectors.
No sample metadata fields
View SamplesRat kidney in normo- and hypotensive animals.
A physiogenomic approach to study the regulation of blood pressure.
No sample metadata fields
View SamplesGata5 is a zinc finger transcription factor that is expressed in embryonic pulmonary mesenchyme and becomes upregulated in the lungs, gut, and bladder during postnatal development. We used microarray to comapre gene expression profiles of mouse lung between Gata5 knockout and wild type mice. We hope to identify the differentially expressed genes that affected by Gata5 gene deletion and their functional clusters or pathways.
Gata5 deficiency causes airway constrictor hyperresponsiveness in mice.
Specimen part
View SamplesWe generated genome-wide RNASeq data from freshly isolated airway epithelial cells of asthmatics and non-asthmatics. This data was paired with genome-wide genetic and methylation data from the same individuals allowing for an integrated analysis of genetic, transcriptional, and epigenetic signatures in asthma. Overall design: examination of genome-wide genome-wide gene expression levels and comparison to phenotypes
DNA methylation in lung cells is associated with asthma endotypes and genetic risk.
Specimen part, Disease, Subject
View SamplesThe goal of this study is to compare tumor-infiltrating antigen presenting cell populations by global transcriptome profiling (RNA-seq) to help further delineate sub-populations of infiltrating myeloid cells in tumor. Methods: Four tumor antigen presenting cell populations were sorted from digested B78chOVA (melanoma variant) tumors in biological triplicate Results: RNA was extracted from the 4 groups (n=3 per group) and prepared for RNAseq. Sequencing yielded ~405 million reads with an average read depth of 33.7 million reads/sample. Reads were then aligned to the mouse genome (UCSC mm10) and those that mapped uniquely to known mRNAs were used to assess differential expression. Overall design: Examination of four tumor infiltrating myeliod populations
Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity.
No sample metadata fields
View SamplesAn experiment was performed to analyze the effect of knockdown of dpf3 during zebrafish embryogenesis.Morpholino against dpf3 and control morpholino were injected into eggs and eggs were kept under standard conditions for 72 hours. Embroys were harvested, total RNA was extracted and used for microarray analysis.
Regulation of muscle development by DPF3, a novel histone acetylation and methylation reader of the BAF chromatin remodeling complex.
Time
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