Notch signaling is widely implicated in mouse mammary gland development and tumorigenesis. To investigate the effects of acute activation of Notch signaling in the mammary epithelial compartment, we generated bi-transgenic MMTV-rtTA; TetO-NICD1 (MTB/TICNX) mice that conditionally express a constitutively active NOTCH1 intracellular domain (NICD1) construct in the mammary epithelium upon doxycycline administration.
Notch promotes recurrence of dormant tumor cells following HER2/neu-targeted therapy.
Sex, Age, Specimen part, Treatment, Time
View SamplesThe cytotoxic drug edelfosine is a synthetic analog of 2-lysophosphatidylcholine. Edelfosine is incorporated by highly proliferating cells, e.g. activated immune cells. It is unknown if the described mechanisms for edelfosine action attained by in vitro approaches exclusively contribute to the observed EAE-amelioration or if edelfosine may exert additional, probably more general and possibly immunoablative effects within the setting of autoimmunity.
The orally available, synthetic ether lipid edelfosine inhibits T cell proliferation and induces a type I interferon response.
Specimen part, Treatment
View SamplesThe origin of biological samples (In vitro infection of HCT-8 cells with Cryptosporidium parvum)
Cryptosporidium parvum regulation of human epithelial cell gene expression.
No sample metadata fields
View SamplesHeterochromatic position effect variegation (PEV) is the epigenetic disruption of genes expression near the new-formed eu-heterochromatic border. We characterized the inversion In(2)A4, demonstrating cis-acting PEV as well as trans-inactivation of the reporter transgenes on the opposite normal chromosome in combination with the inversion. Euchromatic breakpoint of In(2)A4 inversion was localized at 105 bp region (chr2L:21182214-21182318) of the second exon of the Mcm10 gene, the heterochromatic breakpoint is located at the block of dodecasatellite in 2L pericentromeric heterochromatin. In order to check the effects of heterochromatin on neighbor euchromatic genes and estimate the distance of inactivation spreading, we performed RNA-seq analysis of genes expression in larvae and adults females of genotypes A12/A12 (control) and In(2)A4/In(2)A4. Cis-influence of heterochromatin in the inversion causes not only repression, but also activation of genes, and the effects of heterochromatin are different at different developmental stages. Cis-actions affect only a few genes located near the heterochromatin Overall design: Comparison of genes expression in wild type and demonstrating PEV larvae and adults in two repeats each
Trans-inactivation: Repression in a wrong place.
Sex, Subject
View SamplesThe interleukin-23 (IL-23) pathway plays a critical role in the pathogenesis of multiple chronic inflammatory disorders, however, inter-individual variability in IL-23-induced signal transduction in circulating human lymphocytes has not been well-defined. In this study, we observed marked, reproducible inter-individual differences in IL-23 responsiveness (measured by STAT3 phosphorylation) in peripheral blood CD8+CD45RO+ memory T and CD3+CD56+ NKT cells. To define mechanisms that might be contributing to the differential IL-23-induced STAT3 activation between individuals, we examined mRNA expression differences in CD8+CD45RO+ memory T cells between IL-23 responsive and non-responsive individuals.
Age and CD161 expression contribute to inter-individual variation in interleukin-23 response in CD8+ memory human T cells.
Treatment
View SamplesWe identified DNAPK as one of the major proteins that physically interact with Autoimmune regulator (Aire). To establish physiological significance of DNAPK in Aire-driven expression of PTA genes in MECs, we utilized BM-reconstituted SCID mice (which express non functional DNAPK in their MECs) and RAG1 null mouse as a control.
Aire's partners in the molecular control of immunological tolerance.
Specimen part
View SamplesLong-lasting activation of T cells requires up-regulation of many genes, for example of transcription factors, cytoskeletal proteins and cell surface proteins encluding ion channels. An increase of ion channel density at the cell surface reflects the needs to manage increased Ca2+ influx into the activated T cell. Using oligonucleotide-based arrays we have surveyed changes in ion channel mRNA expression that occur upon T cell activation. We used Affymetrix Analysis to confirmate our data achieved by self-designed glass array analysis.
A truncation variant of the cation channel P2RX5 is upregulated during T cell activation.
No sample metadata fields
View SamplesGlobal gene expression studies were performed to determine whether the granulocytic-like MDSC populations from G-CSF treated mice resembled those of tumor-bearing (TB) mice more so than those of the non-tumor-bearing control (i.e., WT) at a molecular level.
Tumor-derived G-CSF facilitates neoplastic growth through a granulocytic myeloid-derived suppressor cell-dependent mechanism.
Sex, Specimen part
View SamplesTo analyze the impact of Aire on gene expression profile in a model cell line, we used 293T cells and transfected them either with an Aire expression plasmid pCMV-Aire (where mAire is driven by CMV promoter) or with a control plasmid pCMV2B.
Aire's partners in the molecular control of immunological tolerance.
Specimen part
View SamplesFormation of the blood from self-renewing hematopoietic stem cells to terminal lineages necessarily involves epigenomic modifications of the genome to control regulator and signature gene expression. By analysing the global expression profiles of hematopoietic stem cells (HSCs), in vivo differentiated CD4+ T cells and CD19+ B cells as well as in vitro differentiated erythrocyte precursor cells, we identified hundreds of transcripts showing type-specific expression in these cell types. To understand the epigenomic changes related to tissue-specific expression during HSC differentiation, we examined the genome-wide distribution of H3K4me1, H3K4me3, H3K27me1, H3K27me3, histone variant H2A.Z, chromatin remodeler BRG1, and RNA Polymerase II in the same four cell types, as well as embryonic stem cells. Analysis of these datasets revealed that numerous key differentiation genes are primed for expression by Brg1 and Pol II binding, as well as bivalent modifications in the HSCs prior to their expression in downstream differentiated cell types. Much of this bivalency in HSC is retained from embryonic stem cells. After differentiation, these modified regions resolve to active chromatin modification configuration in the specific lineage, while in parallel differentiated lineages the bivalent modification remains; Pol II and Brg1 are lost in closer lineages but bivalency resolves to silent monovalency in more distant lineages. Correlation of tissue-specific gene expression with the epigenomic changes predicts tens of thousands of potential common enhancers and tissue-specific enhancers, which may critically contribute to the expression patterns. We provide a valuable dataset for further understanding the regulatory mechanisms of differentiation and function of blood lineages. Overall design: RNA-Seq: This submission comprises RNA-Seq profiling of in vivo differentiated human B cells and hematopoietic stem cells. Re-analyzed data for three cell types: The HSCs were previously uploaded as GSM651554 (SRX037948), but processed differently for this upload. The erythrocyte precursors and T cells have also been previously uploaded as GSM651555 (SRX037949) and GSM406414 (SRX005317), respectively. They were treated as in GSM651554, but processed as here. The processed files generated by our re-analysis are linked below as supplementary files.
Dynamic regulation of epigenomic landscapes during hematopoiesis.
Specimen part, Subject
View Samples