Homologue of Enhancer-of-split 1 (Hes1) is a transcription factor that regulates neuronal plasticity, promoting the growth of dendrites and increasing the GABAergic input. A higher expression of Hes1 also results in neuronal resistance against the noxious activity of amyloid beta, the main agent in the advent and progression of the Alzheimer's disease. As a transcription factor, Hes1 controls de expression of many genes. Using the microarray technology we have detected that the expression of one secreted synaptic protein, cerebellin 4 (Cbln4) was particularly increased upon overexpression of Hes1. We also present evidence that Cbln4 plays an essential role in the formation and maintenance of inhibitory GABAergic connections and that either overexpression of Cbln4 in cultured hippocampal neurons or the application of recombinant Cbln4 to the cultures increased the number of GABAergic varicosities and rescued neurons from amyloid beta induced cell death.
Cerebellin 4, a synaptic protein, enhances inhibitory activity and resistance of neurons to amyloid-β toxicity.
Specimen part
View SamplesBreast cancer (BC) is the most commonly diagnosed neoplasm in women worldwide and a well-recognized heterogeneous pathology classified into four molecular subtypes: Luminal A, Luminal B, HER2-enriched and Basal-like, each one with different biological and clinical characteristics. It is well recognize that clinical and molecular heterogeneity of BC is driven in part by mRNA and lncRNAs. We profiled mRNAs and lncRNA in 75 adjuvant tumors using an Affymetrix microarray platform.
A lncRNA landscape in breast cancer reveals a potential role for AC009283.1 in proliferation and apoptosis in HER2-enriched subtype.
Specimen part
View SamplesWe have generated “reprogrammable” transgenic mice that ubiquitously express the four Yamanaka factors in an inducible manner. Transitory induction of the transgene results in multiple teratomas emerging from a variety of organs, thus indicating that full reprogramming into iPSCs can occur in vivo. By performing bone marrow transplant experiments, we demonstrate that both hematopoietic cells, as well as non-hematopoietic cells can be reprogrammed in vivo. Remarkably, reprogrammable mice also present circulating iPSCs in the bloodstream (in vivo-iPSCs) with all the expected properties of bona fide iPSCs. Moreover, in contrast to in vitro-iPSCs or embryonic stem cells (ESCs), in vivo-iPSCs have an increased capacity to undergo trophectoderm lineage differentiation, which suggests that in vivo-iPSCs are more plastic or primitive than in vitro-generated iPSCs or ESCs. Overall design: 6 clones of in vivo-generated iPSCs, 5 indendent clones of in vitro-generated iPSCs, and 3 clones of established ESCs
Reprogramming in vivo produces teratomas and iPS cells with totipotency features.
Specimen part, Cell line, Subject
View SamplesWe silenced lncRNA AC009283.1 using shRNAs in cell line SKBR3, carried a ~75% silencing compared to thenegative control (NC).
A lncRNA landscape in breast cancer reveals a potential role for AC009283.1 in proliferation and apoptosis in HER2-enriched subtype.
Cell line
View SamplesGene expression profiling of the inferior and superior wall of the distal midgestation arterial domain (outflow tract) of the wild type CD1 mouse embryonic heart
Tbx1 coordinates addition of posterior second heart field progenitor cells to the arterial and venous poles of the heart.
Specimen part
View SamplesPurpose: Here we demonstrate ALK3Bright/PDX1+ cells residing within the human pancreatic ducts have progenitor like characteristics. Using flow cytometery, live-cell sorting of ALK3bright/PDX1+ cells is possible using a surrogate surface marker for PDX1 (P2RY1). Treating ALK3bright/P2RY1+ cells with BMP7 results in their expansion. Later removal of BMP7 results in the differentiation of these cells to ß-like cells. Here we compare the mRNA expression profiles of these three different cell types (in triplicate). Methods: mRNA profiles of ALK3Bright/P2RY1+ cells isolated from human non-endocrine pancreatic tissue, ALK3Bright/P2RY1+ cells treated with BMP7 and ALK3Bright/P2RY1+ cells differentiated to ß-like cells after BMP7 removal were generated by deep sequencing, in triplicate, using Illumina HiSeq PE Cluster Kit v4 and Illumina HiSeq Flow Cell v4 with 50 nt paired end reads plus dual index reads using the Illumina HiSeq SBS kit v4. Sequence reads that passed quality filters were analyzed at the transcript isoform level following alignment using TopHat v2.1.0 followed by exon and gene level counting using Bioconductor easyRNASeq v 2.4.7. Conclusions: Our study represents the first detailed analysis of ALK3Bright/P2RY1+ sorted cells with biological replicates. We demonstrate ALK3Bright/P2RY1+ cells were shown to form progenitor-like epithelial colonies characterized by NKX6.1 and PDX1 expression. Unlike the negative fraction controls, these colonies responded to BMP-7 by generating new ß-like cells as well as cells from other pancreatic lineages. The transcriptional profile of these cells and their BMP7 treated counterparts suggest a mitotic and progenitor like state. Our studies confirm the progenitor-like nature of ALK3Bright/PDX1+ cells within the human pancreas and suggest a specific anatomical location within the ductal network. Overall design: Comparison of transcriptional expression in Alk3Bright/P2RY1+ cells, Alk3Bright/P2RY1+ cells treated with BMP7 and Alk3Bright/P2RY1+ cells allowed to differentiate after BMP7 removal. Human islets, isolated from the same donors were included as a control.
P2RY1/ALK3-Expressing Cells within the Adult Human Exocrine Pancreas Are BMP-7 Expandable and Exhibit Progenitor-like Characteristics.
Specimen part, Subject
View SamplesPrevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, along with inflammation progression, treatment is increasingly complex and expensive. Profilin sensitization constitutes a good model to study the progression of allergic inflammation.
Multi-omics analysis points to altered platelet functions in severe food-associated respiratory allergy.
Specimen part
View SamplesCdk4/6 inhibitors have shown to increase overall survival in hormone-positive breast tumors, but whether other solid tumors could respond to these inhibitors has not yet defined. Here we show that Palbociclib (a Cdk4/6 specific inhibitor in clinic use) treatment exerts antiproliferative effects in vivo using a bladder cancer cell lines.
CDK4/6 Inhibitor as a Novel Therapeutic Approach for Advanced Bladder Cancer Independently of <i>RB1</i> Status.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Lmo2 expression defines tumor cell identity during T-cell leukemogenesis.
Age, Specimen part, Disease, Disease stage
View SamplesIn order to understand the underlying mechanisms, which ensure that disease progression is prevented in EC, a comprehensive analysis of clinical phenotypes coupled to genetics and biomolecular mechanisms is required. The rapidly increasing accessibility of genetic and biomolecular expression data from new high-throughput technologies is the foundation to shift the traditional phenotype-first approach to explorative genetic or molecular data-first approaches. In this study, we aimed to explore a comprehensive analysis of host transcriptomics and proteomics data coupled to clinical phenotypes in a well-defined Swedish EC cohort with up to 20 years of clinical follow-up data.
Transcriptomics and Targeted Proteomics Analysis to Gain Insights Into the Immune-control Mechanisms of HIV-1 Infected Elite Controllers.
Sex, Age, Specimen part, Disease, Treatment, Race
View Samples