T cell-specific transgenic expression of microRNA-181d reduced number of immature CD4+CD8+ thymocytes.
Transgenic expression of microRNA-181d augments the stress-sensitivity of CD4(+)CD8(+) thymocytes.
Specimen part
View SamplesNotch 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 SamplesGATA3 is indispensable for the development of all IL-7Ra-expressing innate lymphoid cells (ILCs) and maintenance of type 1 ILCs (ILC1s) and type 2 ILCs (ILC2s). However, the importance of low GATA3 expression in type 3 ILCs (ILC3s) is still elusive. Here, we report that GATA3 regulates homeostasis of ILC3s by controlling IL-7Ra expression. In addition, GATA3 is critical for the development of NKp46+ ILC3 subset partially through regulating the balance between T-bet and ROR?t. Genome-wide analyses indicate that while GATA3 positively regulates CCR6+ and NKp46+ ILC3 subset-specific genes in respective lineages, it negatively regulates CCR6+ ILC3-specific genes in NKp46+ ILC3s. Furthermore, GATA3 regulates IL-22 production in both CCR6+ and NKp46+ ILC3s. Thus, low GATA3 expression is critical for the development and function of ILC3 subsets. Overall design: To identify GATA3 regulated genes in total ILC3s with RNA-Seq; To identify unique genes expressed by CCR6+ ILC3 or NKp46+ ILC3 and GATA3 regulated genes within these two ILC3 subsets with RNA-Seq; To identify GATA3 direct binding sites in ILC3s, ILC2s and Th2 cells with ChIP-Seq.
Group 3 innate lymphoid cells continuously require the transcription factor GATA-3 after commitment.
No sample metadata fields
View SamplesMicroarray analysis of parity induced gene expression changes in the mammary glands of four strains of rats to identify a common gene signature associated with protection against methylnitrosourea induced mammary tumorigenesis.
Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by pregnancy.
Age, Specimen part
View SamplesCD4(+)Foxp3(+) regulatory T (Treg) cells originate primarily from thymic differentiation, but conversion of mature T lymphocytes to Foxp3 positivity can be elicited by several means, including in vitro activation in the presence of TGF-beta. Retinoic acid (RA) increases TGF-beta-induced expression of Foxp3, through unknown molecular mechanisms. We showed here that, rather than enhancing TGF-beta signaling directly in naive CD4(+) T cells, RA negatively regulated an accompanying population of CD4(+) T cells with a CD44(hi) memory and effector phenotype. These memory cells actively inhibited the TGF-beta-induced conversion of naive CD4(+) T cells through the synthesis of a set of cytokines (IL-4, IL-21, IFN-gamma) whose expression was coordinately curtailed by RA. This indirect effect was evident in vivo and required the expression of the RA receptor alpha. Thus, cytokine-producing CD44(hi) cells actively restrain TGF-beta-mediated Foxp3 expression in naive T cells, and this balance can be shifted or fine-tuned by RA.
Retinoic acid enhances Foxp3 induction indirectly by relieving inhibition from CD4+CD44hi Cells.
Specimen part
View SamplesWe performed RNAseq on subpopulations of mammary epithelial cells. We carried out sorting of a gradient of s-SHIP positive cells in the mammary gland (neg, low, and hi for s-SHIP eGFP). High sSHIP-eGFP populations denote a postulated stem cell population, while low and negative represent more differentiated cell types. s-SHIP eGFP hi to negative potentially represents a gradient from stem to more differentiated progeny, respectively, within the basal epithelial compartment. We FACS sorted 3 replicates for each cell type to represent s-SHIP-neg, s-SHIP-low, and s-SHIP-high. Overall design: We FACS sorted 3 replicates for each cell type to represent s-SHIP-neg, s-SHIP-low, and s-SHIP-high, profiling each of these groups using RNA sequencing.
WNT-Mediated Regulation of FOXO1 Constitutes a Critical Axis Maintaining Pubertal Mammary Stem Cell Homeostasis.
Cell line, Subject
View SamplesIn support of our manuscript investigating the roles of ILCs and T cells in the maintenance of gut hoemostasis, we have performed RNAseq on terminal illeum of mice lacking either all adaptive immune cells (RAG1 -/-), deficient in T cells (TCRalpha -/-), or deficient in T cells but co-housed with wild-type mice and RAG1 -/- mice. Overall design: Tissues from three mice per group were analysed, and the following comparisions were made: RAG1-/- vs. WT C57BL/6 and TCRa-/- co-housed vs TCRa-/- seperately housed. Differential expression genes were identified at 1% FDR using DESeq2.
Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism.
Subject
View SamplesGene expression data indicate an early up-regulation of inflammatory and fibrotic remodeling pathways in DSC2 transgenic mice vs. non-transgenic control mice. The mice were analyzed at the age of 3.5 and 13 weeks.
Transgenic mice overexpressing desmocollin-2 (DSC2) develop cardiomyopathy associated with myocardial inflammation and fibrotic remodeling.
Age, Specimen part
View SamplesA comparison of gene expression in the mammary gland of lactating mice at day 9 after parturition between Akt -/- and wildtype individuals.
Isoform-specific requirement for Akt1 in the developmental regulation of cellular metabolism during lactation.
Sex, Age, Specimen part, Subject
View SamplesDisplacement of Bromodomain and Extra-Terminal (BET) proteins from chromatin has promise for cancer and inflammatory disease treatments, but roles of BET proteins in metabolic disease remain unexplored. Small molecule BET inhibitors, such as JQ1, block BET protein binding to acetylated lysines, but lack selectivity within the BET family (Brd2, Brd3, Brd4, Brdt), making it difficult to disentangle contributions of each family member to transcriptional and cellular outcomes. Here, we demonstrate multiple improvements in pancreatic -cells upon BET inhibition with JQ1 or BET-specific siRNAs. JQ1 (50-400 nM) increases insulin secretion from INS-1 cells in a concentration dependent manner. JQ1 increases insulin content in INS-1 cells, accounting for increased secretion, in both rat and human islets. Higher concentrations of JQ1 decrease intracellular triglyceride stores in INS-1 cells, a result of increased fatty acid oxidation. Specific inhibition of both Brd2 and Brd4 enhances insulin transcription, leading to increased insulin content. Inhibition of Brd2 alone increases fatty acid oxidation. Overlapping yet discrete roles for individual BET proteins in metabolic regulation suggest new isoform-selective BET inhibitors may be useful to treat insulin resistant/diabetic patients. Results imply that cancer and diseases of chronic inflammation or disordered metabolism are related through shared chromatin regulatory mechanisms.
BET Bromodomain Proteins Brd2, Brd3 and Brd4 Selectively Regulate Metabolic Pathways in the Pancreatic β-Cell.
Cell line
View Samples