Nonsense-mediated RNA decay (NMD) is a highly conserved pathway that selectively degrades specific subsets of RNA transcripts. Here, we provide evidence that NMD regulates early human developmental cell fate. We found that NMD factors tend to be expressed at higher levels in human pluripotent cells than differentiated cells, raising the possibility that NMD must be downregulated to permit differentiation. Loss- and gain-of-function experiments in human embryonic stem cells (hESCs) demonstrated that, indeed, NMD downregulation is essential for efficient generation of definitive endoderm. RNA-seq analysis identified NMD target transcripts induced when NMD is suppressed in hESCs, including many encoding signaling components. This led us to test the role of TGF-b and BMP signaling, which we found NMD acts through to influence definitive endoderm vs. mesoderm fate. Our results suggest that selective RNA decay is critical for specifying the developmental fate of specific human embryonic cell lineages. Overall design: Examination of differential gene expression in hESCs upon loss of UPF1.
Nonsense-Mediated RNA Decay Influences Human Embryonic Stem Cell Fate.
Specimen part, Cell line, Subject
View SamplesSelection of B cells subjected to hypermutation in germinal centres (GC) during T-dependent (TD) antibody responses yields memory cells and long-lived plasma cells that produce high affinity antibodies biased to foreign antigens rather than self-antigens. GC also form in T-independent (TI) responses to polysaccharide antigens but failed selection results in GC involution and memory cells are not generated. To date there are no markers that allow phenotypic distinction of T-dependent and T-independent germinal centre B cells. We have now compared the global gene expression of GC B cells purified from mice immunized with either TD or TI antigens and identified eighty genes that are differentially expressed in TD GC.
Axon growth and guidance genes identify T-dependent germinal centre B cells.
No sample metadata fields
View SamplesThe skin is a protective barrier against external insults and any lesion must be rapidly and efficiently repaired. Dermal fibroblasts are the major source of extracellular connective tissue matrix and play an important role in wound healing. Vitamin C is an important water-soluble free radical scavenger and an essential cofactor for collagen synthesis by dermal fibroblasts and, consequently, may contribute to the maintenance of healthy skin. Using microarray analysis, we investigated the effects of long-term exposure to a stable vitamin C derivative, ascorbic acid 2-phosphate (AA2P), in contact-inhibited populations of primary human dermal fibroblasts. Compared with "scorbutic" cells, cells exposed to AA2P increased the expression of genes associated with DNA replication and repair and with the G(2)/M phase of the cell cycle. Consistent with the gene expression changes, AA2P increased the mitogenic stimulation of quiescent fibroblasts by serum factors and cell motility in the context of wound healing. Furthermore, AA2P-treated fibroblasts showed faster repair of oxidatively damaged DNA bases. We propose that vitamin C may protect the skin by promoting fibroblast proliferation, migration, and replication-associated base excision repair of potentially mutagenic DNA lesions, and we discuss the putative involvement of hypoxia-inducible transcription factor-1 and collagen receptor-related signaling pathways.
Gene expression profiling reveals new protective roles for vitamin C in human skin cells.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrated epigenome profiling of repressive histone modifications, DNA methylation and gene expression in normal and malignant urothelial cells.
Specimen part, Cell line
View SamplesTo gain a more depth knowledge of repressive epigenetic gene regulation in UCC, we have profiled H3K9m3 and H3K27m3 in normal and malignant urothelial cells. We matched these profiles to those 5-methylcytosine and gene expression. We hypothesized that differences represent pro-carcinogenic events within the urothelium.
Integrated epigenome profiling of repressive histone modifications, DNA methylation and gene expression in normal and malignant urothelial cells.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Binding loci of RelA-containing nuclear factor-kappaB dimers in promoter regions of PHM1-31 myometrial smooth muscle cells.
Specimen part
View SamplesA study to define the binding loci of RelA-containing NF-kappaB dimers and subsequent correlation with gene expression in a human myometrial smooth muscle cell line after exposure to TNF.
Binding loci of RelA-containing nuclear factor-kappaB dimers in promoter regions of PHM1-31 myometrial smooth muscle cells.
Specimen part
View SamplesAnalysis of the gene expression level of 4T1 orthotopic tumors in mice with and without pericyte depletion.
Targeting vascular pericytes in hypoxic tumors increases lung metastasis via angiopoietin-2.
Specimen part, Treatment
View SamplesHuman ES or iPS Cells were differentiated into endothelial cells (ECs) defined by expression of CD31 (PECAM1) and CD144 (VE-Cadherin) on the cell surface. All ES or iPS derived ECs were greater than 90% double positive for these two markers.
Limited gene expression variation in human embryonic stem cell and induced pluripotent stem cell-derived endothelial cells.
Specimen part
View SamplesTRAP-seq gene expression profiling. GFP-L10a is expressed in BDNF+ or PACAP+ in preoptic area. Bdnf+ or Pacap+ cells in the preoptic area are labelled with GFP-L10a fusion protein expression to study cell-type specific gene expression. We used adult BDNF-Cre (custom generated, discussed in submitted paper) and Pacap-Cre mice (Allen Brain Institute, gift Hongkui Zeng) and injected Cre-depndent adenoassociated virus (AAV2-EF1a-DIO-EGFP-L10a, custom made) into the ventromedial preoptic area. Overall design: Comparison of Immunoprecipitation and Input fraction mRNA
Warm-Sensitive Neurons that Control Body Temperature.
Specimen part, Cell line, Subject
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