In the past decade, several transcription factors critical for pancreas development have been identified. Despite this success, many of the cell surface and extracellular factors necessary for proper islet morphogenesis and function remain uncharacterized. Previous studies have shown that transgenic over-expression of the transcription factor HNF6 specifically in the pancreatic endocrine cell lineage resulted in the disruption of islet morphogenesis, including dysfunctional endocrine cell sorting, increased islet size, and failure of islets to migrate away from the ductal epithelium. We exploited the dysmorphic islets in pdx1PBHnf6 animals as a tool to identify factors important for islet morphogenesis. Genome-wide microarray analysis was used to identify differences in the gene expression profiles of late gestation and early postnatal pancreas tissue from wild type and pdx1PBHnf6 animals. We report the identification of genes with an altered expression in HNF6 Tg animals and highlight factors with potential importance in islet morphogenesis.
Gene expression profiling of a mouse model of pancreatic islet dysmorphogenesis.
Specimen partView Samples
The discovery of genetic variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster associated with heavy smoking and higher relapse risk has led to the identification of the midbrain habenula- interpeduncular axis as a critical relay circuit in the control of nicotine addiction
Reexposure to nicotine during withdrawal increases the pacemaking activity of cholinergic habenular neurons.
Specimen part, DiseaseView Samples
Background In flowering plants, the anther is the site of male gametophyte development. Two major events in the development of the male germline are meiosis and the asymmetric division in the male gametophyte that gives rise to the vegetative and generative cells, and the following mitotic division in the generative cell that produces two sperm cells. Anther transcriptomes have been analyzed at progressive stages of development by using microarray and sequence by synthesis technologies to identify genes that regulate anther development. Here we have carried out a comprehensive analysis of rice anther transcriptomes at four distinct stages of development with a focus to identify regulatory components contributing to male meiosis and germline development. Further, these transcriptomes have been compared with transcriptomes of 10 stages of rice vegetative and seed development to identify genes that express specifically during anther development. Results - To understand the molecular processes that lead to male gametophyte development, transcriptome profiling of four stages of anther development in rice [pre-meiotic (PMA), meiotic (MA), anthers at single-celled (SCP) and tri-nucleate pollen (TPA)] was conducted. Around 22,000 genes were found to be expressed in at least one of the anther developmental stages, with the highest number in MA (18,090) and lowest (15,465) in TPA. Comparison of these transcriptome profiles to an in-house generated microarray-based transcriptomics database comprising of 10 stages/tissues of vegetative as well as reproductive development in rice resulted in the identification of1,000 genes that are specifically expressed in anther stages. Of them the expression of 453 genes was found to be specific to TPA, whereas 78 and 184 genes were expressed specifically in MA and SCP. Gene ontology and pathway analysis of specifically expressed genes revealed that transcription factors and protein folding, sorting and degradation pathway genes dominated in MA, whereas in TPA, those coding for cell structure and signal transduction components were in abundance. Interestingly, about 50% of the genes with anther-specific expression have not been annotated so far. Conclusions - These data not only provide the transcriptome constituents of four landmark stages of anther development but also identify genes that express exclusively in these stages and therefore may contribute to specific aspects of anther and/or male gametophyte development in rice. Moreover, these gene sets assist in building a deeper understanding of underlying regulatory networks and in selecting candidates for gene function validation.
Analysis of anther transcriptomes to identify genes contributing to meiosis and male gametophyte development in rice.
Specimen partView Samples
Our understanding of the mechanisms that govern the cellular process of meiosis is limited in higher plants with polyploid genomes. Bread wheat is an allohexaploid that behaves as a diploid during meiosis. Chromosome pairing is restricted to homologous chromosomes despite the presence of homoeologues in the nucleus. The importance of wheat as a crop and the extensive use of wild wheat relatives in breeding programs has prompted many years of cytogenetic and genetic research to develop an understanding of the control of chromosome pairing and recombination. The rapid advance of biochemical and molecular information on meiosis in model organisms such as yeast provides new opportunities to investigate the molecular basis of chromosome pairing control in wheat. However, building the link between the model and wheat requires points of data contact. We report here a large-scale transcriptomics study using the Affymetrix wheat GeneChip aimed at providing this link between wheat and model systems and at identifying early meiotic genes. Analysis of the microarray data identified 1,350 transcripts temporally-regulated during the early stages of meiosis. Expression profiles with annotated transcript functions including chromatin condensation, synaptonemal complex formation,recombination and fertility were identified. From the 1,350 transcripts, 30 displayed at least an eight-fold expression change between and including pre-meiosis and telophase II, with more than 50% of these having no similarities to known sequences in NCBI and TIGR databases. This resource is now available to support research into the molecular basis of pairing and recombination control in the complex polyploid, wheat.
Microarray expression analysis of meiosis and microsporogenesis in hexaploid bread wheat.
Specimen partView Samples
The therapy-induced PML/RARA catabolism elicits the loss of APL-initiating cell self-renewal through PML NB reformation and P53 activation. These results explain the curative activity of the RA/arsenic combination, the resistance to RA of PLZF/RARA-driven APLs and they raise the prospect that activation of this PML/P53 checkpoint might have therapeutic values in other malignancies.
Activation of a promyelocytic leukemia-tumor protein 53 axis underlies acute promyelocytic leukemia cure.
Specimen part, Treatment, TimeView Samples
T cells exhibit an intensified STING response, which leads to the expression of a distinct set of genes and results in the induction of apoptosis Overall design: CD4+ T cells were stimulated either with DMSO or 10-carboxymethyl-9-acridanone (CMA) for 16 hours. RNA was isolated for analysis.
Signalling strength determines proapoptotic functions of STING.
Specimen part, Cell line, SubjectView Samples
The PLZF-RARa fusion oncoprotein is overexpressed in the t(11;17) subtype of acute promyelocytic leukemia. Gene expression microarrays were used to identify genes involved in leukemic transformation.
Comprehensive genomic screens identify a role for PLZF-RARalpha as a positive regulator of cell proliferation via direct regulation of c-MYC.
Cell lineView Samples