Activation of b-catenin has been causatively linked to the etiology of colon cancer. Conditional stabilization of this molecule in pro-T-cells promotes thymocyte development without the requirement for preTCR signaling. We show here that activated b-catenin stalls the developmental transition from the double-positive (DP) to the single-positive (SP) thymocyte stage and predisposes DP thymocytes to transformation. b-Catenin induced thymic lymphomas have a leukemic arrest at the early DP stage. Lymphomagenesis requires Rag activity, which peaks at this developmental stage, as well as additional secondary genetic events. A consistent secondary event is the transcriptional upregulation of c-Myc, whose activity is required for transformation since its conditional ablation abrogates lymphomagenesis. In contrast, the expression of Notch receptors as well as targets is reduced in DP thymocytes with stabilized b-catenin and remains low in the lymphomas indicating that Notch activation is not required or selected for in b-catenin induced lymphomas. Thus, b-catenin activation may provide a mechanism for the induction of T-ALL that does not depend on Notch activation.
Beta-catenin stabilization stalls the transition from double-positive to single-positive stage and predisposes thymocytes to malignant transformation.
No sample metadata fields
View SamplesExpression profiling of cortex from embryonic day (E) 17.5 telencephalon of Sox11(+/+) and Sox11(-/-) mouse embryos. Sox11 is implicated in regulating proliferation, neuronal migration and differentiation.
Transcription factor Sox11 is essential for both embryonic and adult neurogenesis.
Specimen part
View SamplesUsing cell-free fetal RNA from amniotic fluid supernatant samples, the gene expression profiles of fetuses with varying FMR1 5 UTR CGG repeat lengths were compared to gestational age- and sex-matched controls. Broad patterns of genome-wide expression changes were identified when comparing fetuses with expanded FMR1 alleles to those with normal length FMR1 alleles. Genes with altered expression include those related to ubiquitination, mitochondrial function and neuronal/synaptic architecture as well as genes previously linked to other intellectual disabilities and abnormalities of motor function.
No associated publication
Sex
View SamplesTo identify molecular pathophysiologic changes and novel disease mechanisms specific to myelomeningocele by analyzing AFS cfRNA in fetuses with open myelomeningocele.
Amniotic fluid transcriptomics reflects novel disease mechanisms in fetuses with myelomeningocele.
No sample metadata fields
View SamplesWe used a smooth muscle cell-specific mineralocorticoid receptor knockout mouse to generate young and aged MR-intact and SMC-MR-KO aortic mRNA to examine the effect of age on vascular mRNA alterations in the presence and absence of SMC-MR.
Smooth Muscle Cell-Mineralocorticoid Receptor as a Mediator of Cardiovascular Stiffness With Aging.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNA-Offset RNA Alters Gene Expression and Cell Proliferation.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
RNA-Seq and expression microarray highlight different aspects of the fetal amniotic fluid transcriptome.
Sex
View SamplesIschemic heart failure after acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. We recently reported that activation of a trans-valvular axial-flow pump in the LV and delaying myocardial reperfusion, known as Primary Unloading, limits infarct size by reducing LV wall stress and increasing expression of the cardioprotective cytokine, stromal derived factor 1 alpha (SDF1a). The mechanisms underlying the cardioprotective benefit and sustained effect of Primary Unloading remain poorly understood. We now tested the importance of delayed reperfusion, the functional significance of SDF1a, and the late-term impact on myocardial function and scar size associated with Primary Unloading.
Left Ventricular Unloading Before Reperfusion Promotes Functional Recovery After Acute Myocardial Infarction.
Sex, Specimen part, Treatment
View SamplesMicroRNA-offset RNAs (moRs) were first identified in simple chordates and subsequently in mouse and human cells by deep sequencing of short RNAs. MoRs are derived from sequences located immediately adjacent to microRNAs (miRs) in the primary miR (pri-miR). Currently moRs are considered to be simply a by-product of miR biosynthesis that lack biological activity. Here we show for the first time that a moR is biologically active. We now demonstrate that endogenous and over-expressed moR-21 significantly alters gene expression and inhibits the proliferation of vascular smooth muscle cells (VSMC). We report that the seed region of moR-21 as well as the seed match region in the target gene 3'UTR are indispensable for moR-21-mediated gene down-regulation. We further demonstrated that moR-21-mediated gene repression is Argonaute 2 (Ago2) dependent. In addition, we find that miR-21 and moR-21 may regulate different genes in a given pathway and can oppose each other in regulating certain genes. Taken together, these findings provide the first evidence that microRNA offset RNA regulates gene expression and is biologically active.
MicroRNA-Offset RNA Alters Gene Expression and Cell Proliferation.
Specimen part, Treatment
View SamplesThe second trimester fetal transcriptome can be assessed based on cell-free RNA found within the amniotic fluid supernatant. The objective of this study was to compare the suitability of two technologies for profiling the human fetal transcriptome: RNA-Seq and expression microarray. Comparisons were based on total numbers of gene detected, rank-order gene expression, and functional genomic analysis.
RNA-Seq and expression microarray highlight different aspects of the fetal amniotic fluid transcriptome.
Sex
View Samples