CNS autoimmunity is induced by autoreactive T cells reactive against CNS antigen. However how these T cells become able to transgress the blood brain barrier is not CNS autoimmunity is induced by autoreactive T cells reactive against CNS antigen. Here a gene expression profile of the pathogenic T cells in different functional states was performed.
T cells become licensed in the lung to enter the central nervous system.
Sex, Specimen part
View SamplesThe role of microRNAs (miRNA) in first cell fate choice of the preimplantation mouse embryo remains unresolved, as gene expression and knockout data are conflicting. This cell fate choice generates the extraembryonic lineage of the trophoblast and the embryonic lineage of the epiblast (inner cell mass). The trophoblast differentiates into polar and mural cells, where polar cells contribute to placental development and mural cells to the implantation process and Reicherts membrane. The inner cell mass further differentiates into the epiblast and primitive endoderm. We used stem cell lines that can be derived from the trophoblast and epiblast lineages to address the role of miRNAs in early lineage cell fate specification and determination. Using embryonic stem cells (ESC) and trophoblast stem cells (TSC) as starting and ending states of cell development we identified a network of TSC expressed miRNAs that are enriched in ESC targets mRNA. We used constitutive and inducible expression of TSC enriched miRNAs in ESC and show that they can drive cell morphology and gene expression profiles similar to trophoblast. Additionally we show that this process required HDAC2 inhibition and is miRNA specific, as cardiac specific miR-1 could not induce trophoblast under these conditions. In contrast to embryo derived and Cdx2 induced trophoblast cells, miRNAs promote a mural TE like cell phenotype. Transplantation into preimplantation mouse embryos showed that miRNA-induced trophoblast preferentially contributes to the mural trophoblast in both the blastocyst and the Reicherts membrane. Our data support a role for miRNAs and HDACs in the specification of the trophoblast and potentially the polar and mural cell types.
Overexpression of Trophoblast Stem Cell-Enriched MicroRNAs Promotes Trophoblast Fate in Embryonic Stem Cells.
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View SamplesThe Akita mutation (C96Y) in the insulin gene results in early onset diabetes in both humans and mice. Expression of the mutant proinsulin (C96Y) causes endoplasmic reticulum (ER) stress in pancreatic -cells and consequently the cell activates the unfolded protein response (UPR). Since the proinsulin is terminally misfolded however, the ER stress is irremediable and chronic activation of the UPR eventually activates apoptosis in the cell population.
IRE1 inhibition perturbs the unfolded protein response in a pancreatic β-cell line expressing mutant proinsulin, but does not sensitize the cells to apoptosis.
Specimen part, Cell line
View SamplesWe performed RNA-seq to quantify gene expression changes in adult worms upon knockdown of transcription factor unc-62/Homothorax. unc-62 is a developmental regulator that binds proximal to age-regulated transcripts and modulates lifespan. In the intestine (in which tissue-specific unc-62 knockdown increases lifespan), we identify multiple effects of unc-62 knockdown linked to extension of longevity. First, unc-62 RNAi decreases the expression of yolk proteins (vitellogenins) that aggregate in the body cavity and become toxic in old age. Second, unc-62 RNAi results in a broad increase in expression of intestinal genes that typically decrease expression with age, suggesting that unc-62 activity balances intestinal resource allocation between yolk protein expression and fertility on the one hand and somatic functions on the other. Overall design: mRNA profiling by Illumina HiSeq of 3 biological replicates of day 4 adult Caenorhabditis elegans that were fed either control or unc-62 RNAi beginning at day 1 of adulthood.
Roles of the developmental regulator unc-62/Homothorax in limiting longevity in Caenorhabditis elegans.
Specimen part, Cell line, Subject
View SamplesWe used RNA-seq to discover that gene expression changes during aging are attenuated in elt-2 overexpressors relative to controls Overall design: Whole-worm mRNA was sequenced from worms over-expressing elt-2 and control worms. Five biological replicates were collected for each condition.
Deactivation of the GATA Transcription Factor ELT-2 Is a Major Driver of Normal Aging in C. elegans.
Specimen part, Cell line, Subject
View SamplesTissue morphogenesis relies on proper differentiation of morphogenetic domains, adopting specific cell behaviours. Yet, how signalling pathways interact to determine and coordinate these domains remains poorly understood. Dorsal closure (DC) of the Drosophila embryo represents a powerful model to study epithelial cell sheet sealing. In this process, JNK (JUN N-terminal Kinase) signalling controls leading edge (LE) differentiation generating local forces and cell shape changes essential for DC. The LE represents a key morphogenetic domain in which, in addition to JNK, a number of signalling pathways converges and interacts (anterior/posterior -AP- determination; segmentation genes, such as Wnt/Wingless; TGF/Decapentaplegic). To better characterize properties of the LE morphogenetic domain, we used microarrays to identify genes whose expression is regulated by the JNK pathway during dorsal closure of the Drosophila embryo.
The Drosophila serine protease homologue Scarface regulates JNK signalling in a negative-feedback loop during epithelial morphogenesis.
Specimen part
View SamplesWe used RNA-seq to identify 162 genes that are differentially-regulated following elt-2 RNAi Overall design: Whole-worm mRNA was sequenced from elt-2 RNAi- and control-fed worms. Biological triplicates were assay for each condition
Deactivation of the GATA Transcription Factor ELT-2 Is a Major Driver of Normal Aging in C. elegans.
Specimen part, Cell line, Subject
View SamplesWe used RNA-seq to identify 292 genes that are differentially-regulated following elt-2 RNAi Overall design: Whole-worm mRNA was sequenced from elt-2 RNAi- and control-fed worms. Biological triplicates were assay for each condition
Deactivation of the GATA Transcription Factor ELT-2 Is a Major Driver of Normal Aging in C. elegans.
Specimen part, Cell line, Subject
View SamplesWe used RNA-seq to assay gene expression changes over time in response to OP50 and PY79 To understand the molecular processes underlying aging, we screened modENCODE ChIP-seq data to identify transcription factors that bind to age-regulated genes in C. elegans. The most significant hit was the GATA transcription factor encoded by elt-2, which is responsible for inducing expression of intestinal genes during embryogenesis. Expression of ELT-2 decreases during aging, beginning in middle age. We identified genes regulated by ELT-2 in the intestine during embryogenesis, and then showed that these developmental genes markedly decrease in expression as worms grow old. Overexpression of elt-2 extends lifespan and slows the rate of gene expression changes that occur during normal aging. Thus, our results identify the developmental regulator ELT-2 as a major driver of normal aging in C. elegans. Overall design: Whole-worm mRNA was sequenced from E. coli- and B.subtilis-fed worms. For each condidtion, one replicate was sequenced at Day 4 and Day 13
Deactivation of the GATA Transcription Factor ELT-2 Is a Major Driver of Normal Aging in C. elegans.
Specimen part, Cell line, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Specimen part, Treatment
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