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GSE102137
Mus musculus
17 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene expression in FOXO KO vs WT brain
Publication Title
FOXO protects against age-progressive axonal degeneration.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
AbstractFollicular helper T (Tfh) cells are crucial for germinal center (GC) formation and humoral adaptive immunity. Mechanisms underlying Tfh cell differentiation in peripheral and mucosal lymphoid organs are incompletely understood. We report here that mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for Tfh cell differentiation and GC reaction under steady state and after antigen immunization and viral infection. Loss of mTORC1 and mTORC2 in T cells exerted distinct effects on Tfh cell signature gene expression, whereas increased mTOR activity promoted Tfh responses. Deficiency of mTORC2 impaired CD4+ T cell accumulation and IgA production, and aberrantly induced Foxo1 transcription factor. Mechanistically, the costimulatory molecule ICOS activated mTORC1 and mTORC2 to drive glycolysis and lipogenesis, and Glut1-mediated glucose metabolism promoted Tfh cell responses. Altogether, mTOR acts as a central node in Tfh cells to link immune signals to glucose metabolism and transcriptional activity.
Publication Title
mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
Illumina HiSeq 3000
Description
Effector (Teff) and regulatory (Treg) CD4 T cells undergo metabolic reprogramming to support proliferation and immune function. While Phosphatidylinositide 3-kinase (PI3K)/Akt/mTORC1 signaling induces the glucose transporter Glut1 and aerobic glycolysis for Teff proliferation and inflammatory function, mechanisms that regulate Treg metabolism and function remain unclear. We show that TLR signals that promote Treg proliferation increase Glut1, PI3K/Akt/mTORC1 signaling, and glycolysis. However, TLR-induced mTORC1 signaling also impaired Treg suppressive capacity. Conversely, FoxP3 opposed PI3K/Akt/mTOR signaling to reduce glycolysis and anabolic metabolism while increasing oxidative and catabolic metabolism. Importantly, Glut1 expression was sufficient to increase Treg numbers but reduced suppressive capacity and FoxP3 expression. Thus, inflammatory signals and FoxP3 balance mTORC1 signaling and glucose metabolism to control Treg proliferation and suppressive function. Overall design: RNAseq of induced Glut1 transgenic and control Treg
Publication Title
Foxp3 and Toll-like receptor signaling balance T<sub>reg</sub> cell anabolic metabolism for suppression.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Sel1L is an adaptor protein for the E3 ligase Hrd1 involved in endoplasmic reticulum-associated degradation (ERAD). Its physiological importance in mammalian ERAD, however, remains to be established. Here, using the inducible Sel1L knockout mouse and cell models, we provide the first in vivo evidence that Sel1L is indispensable for Hrd1 stability, ER homeostasis and survival. Acute loss of Sel1L leads to premature death in adult mice within 3 weeks with profound pancreatic atrophy. Contrary to current belief, our data show that mammalian Sel1L is required for Hrd1 stability and ERAD function both in vitro and in vivo. Sel1L deficiency disturbs ER homeostasis, activates ER stress, attenuates translation and promotes cell death. Serendipitously, using biochemical approach coupled with mass spectrometry, we found that Sel1L deficiency causes the aggregation of both small and large ribosomal subunits. Thus, Sel1L is an indispensable component of mammalian ERAD and ER homeostasis, which is essential for protein translation, pancreatic function, cellular and organismal survival.
Publication Title
Sel1L is indispensable for mammalian endoplasmic reticulum-associated degradation, endoplasmic reticulum homeostasis, and survival.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
To identify gene expression changes associated with treatment of EV that carry high levels of miR-105 (from MDA-MB-231 and MCF10A/miR-105 cells) in human breast tumor derived CAF, we analyzed RNA isolated from PBS- or EV-treated CAF. Gene expression in CAF treated with EV from MDA-MB-231 or MCF10A/miR-105 cells was compared to cells treated with PBS or EV from MCF10A cells, both of which served as controls in this experiment. Overall design: RNA was extracted from PBS- and EV-treated CAF, and subjected to library construction and RNA sequencing.
Publication Title
Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC-dependent metabolic reprogramming of stromal cells.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
To identify gene expression changes associated with overexpression of miR-105 or MYC in MCF10A non-cancerous human mammary epithelial cells, we analyzed RNA isolated from engineered MCF10A cell lines that stably express empty vector, GFP, miR-105, or MYC by RNA-seq. Gene expression in cells overexpressing miR-105 or MYC was compared to cells expressing the empty vector or GFP, both of which served as controls in this experiment. Overall design: RNA was extracted from MCF10A cells stably expressing pBabe vector, pBabe-GFP, pBabe-miR-105, or pBabe-MYC; RNA was then subjected to library construction and RNA sequencing.
Publication Title
Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC-dependent metabolic reprogramming of stromal cells.
Sample Metadata Fields
Cell line, Subject
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
In seedlings, the induction of shade avoidance syndrome (SAS) involves a rapid up-regulation for known shade marker genes and subsequently activates an interacting network of various hormones that will eventually lead to cell elongation. We found that the B-box protein AtBBX24 have positive effects on the SAS (positive regulators). Global expression analysis of col and bbx24 seedlings reveals that a large number of genes involved in hormonal signaling pathways are positively regulated by BBX24 in response to simulated shade.
Publication Title
The transcriptional regulator BBX24 impairs DELLA activity to promote shade avoidance in Arabidopsis thaliana.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 3000
Description
Activated T cells differentiate into functional subsets which require distinct metabolic programs. Glutaminase (GLS) converts glutamine to glutamate to provide substrate for the tricarboxylic acid cycle and epigenetic reactions and here we identify a key role for GLS in T cell activation and specification. Though GLS-deficiency diminished T cell activation, proliferation and impaired differentiation of Th17 cells, loss of GLS also increased Tbet and Interferon-? expression and CD4 Th1 and CD8 CTL effector cell differentiation. These changes were mediated by differentially altered gene expression and chromatin accessibility, leading to increased sensitivity of Th1 cells to IL-2 mediated mTORC1 signaling. In vivo, GLS-null T cells failed to drive a Th17-mediated Graft-vs-Host Disease model. Transient inhibition of GLS, however, increased Th1 and CTL T cell numbers in viral and chimeric antigen receptor models. Glutamine metabolism thus has distinct roles to promote Th17 but constrain Th1 and CTL effector cell differentiation. Overall design: Cells were treated with glutaminase1 inhibitor or vehicle
Publication Title
Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To accelerate the development of disease-modifying therapeutics for Huntingtons disease (HD), a dynamic biomarker of disease activity and treatment response is critically needed.
Publication Title
Transcriptional modulator H2A histone family, member Y (H2AFY) marks Huntington disease activity in man and mouse.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The maintenance of advanced malignancies relies on continued activity of driver oncogenes, although their rate-limiting role is highly context-dependent with respect to tumor types and associated genetic alterations. Oncogenic Kras mutation is the signature event in human pancreatic ductal adenocarcinoma (PDAC), serving a critical role in tumor initiation. Here, an inducible KrasG12D-driven p53 mutant PDAC mouse model establishes that advanced PDAC remains strictly dependent on continued KrasG12D expression and that KrasG12D serves a vital role in the control of tumor metabolism, through stimulation of glucose uptake and channeling of glucose intermediates through the hexosamine biosynthesis pathway (HBP) and the pentose phosphate pathway (PPP). Notably, these studies reveal that oncogenic Kras regulates ribose biogenesis. Unlike canonical models of PPP-mediated ribose biogenesis, we demonstrate that oncogenic Kras drives intermediates from enhanced glycolytic flux into the non-oxidative arm of the PPP, thereby decoupling ribose biogenesis from NADPNADPH-mediated redox control. Together, this work provides in vivo mechanistic insights into how oncogenic Kras promotes metabolic reprogramming in native tumors and illuminates potential metabolic targets that can be exploited for therapeutic benefit in Kras-driven PDAC.
Publication Title
Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism.
Sample Metadata Fields
Specimen part, Treatment
View Samples