Nitrogen (N) and nitrate (NO3-) per se regulate many aspects of plant metabolism, growth and development. N/NO3- also suppresses parts of secondary metabolism including anthocyanin synthesis. Molecular components for this repression are unknown. We report that three N/NO3--induced members of the LATERAL ORGAN BOUNDARY DOMAIN (LBD) gene family of transcription factors (LBD37, LBD38 and LBD39) act as negative regulators of anthocyanin biosynthesis in Arabidopsis (Arabidopsis thaliana). Over-expression of each of the three genes in the absence of N/NO3- strongly suppresses the key regulators of anthocyanin synthesis PAP1 and PAP2, genes in the anthocyanin-specific part of flavonoid synthesis, as well as cyanidin- but not quercetin- or kaempferol-glycoside production. Conversely, lbd37, lbd38 or lbd39 T-DNA insertion mutants accumulate anthocyanins when grown in N/NO3--sufficient conditions and show constitutive expression of anthocyanin biosynthetic genes. The LBD genes also repress many other known N-responsive genes including key genes required for NO3- uptake and assimilation, resulting in altered NO3- content, nitrate reductase activity/activation, protein, amino acid and starch levels, and N-related growth phenotypes. The results identify LBD37 and its two close homologs as novel repressers of anthocyanin biosynthesis and N-availability signals in general. They also show that besides being developmental regulators LBD genes fulfill roles in metabolic regulation.
Members of the LBD family of transcription factors repress anthocyanin synthesis and affect additional nitrogen responses in Arabidopsis.
Age, Specimen part, Treatment
View SamplesSTO2 is a novel MYB like protein which belongs to one of the most important transcription factors in planta.
Salt-Related MYB1 Coordinates Abscisic Acid Biosynthesis and Signaling during Salt Stress in Arabidopsis.
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 SamplesRecently, we identified mesenchymoangioblast (MAB), as a clonal mesodermal precursor for mesenchymal and endothelial cells. Here we show, that MABs have the capacity to produce mesenchymal progenitors, which can be differentiated into pericytes or smooth muscles cells under the influence of PDGF-BB or TGFß plus sphingosylphosphorylcholine (SPC), respectively. Based on these studies we established the hierarchy of vasculogenic progenitors that provides the platform for interrogation of molecular mechanisms regulating vasculogenic cell specification and diversification from primitive posterior mesoderm. Overall design: Vasculogenic cells generated under specific culture conditions. Primary cells were used as control.
Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts.
No sample metadata fields
View SamplesUsing global gene expression and proteomic analyses, we identified a molecular signature in human embryonic and induced pluripotent stem cells that suggested a central regulatory role for RNA splicing in self-renewal. Through genetic and biochemical approaches, we established reciprocal functional links between the master regulatory factor OCT4 and SFRS2, a member of the serine/arginine-rich family of splicing factors. SFRS2 regulates expression of two isoforms of the methyl-CpG-binding protein MBD2 that play opposing roles in human ESC and during the reprogramming of fibroblasts. Both the MBD2a isoform expressed in fibroblasts and the MBD2c isoform found in pluripotent cells bind OCT4 and NANOG promoters in human ESC, but only MBD2a interacts with NuRD chromatin remodeling factors. Members of the miR-301 and miR-302 families provide additional regulation by targeting SFRS2 and the somatic specific MBD2a isoform. These data are consistent with a model in which OCT4, SFRS2, and MBD2 participate in a positive feedback loop to regulate proteome diversity in support of self-renewal in pluripotent cells.
Alternative splicing of MBD2 supports self-renewal in human pluripotent stem cells.
Specimen part
View SamplesBrain tumors are among the most malignant cancers and can arise from neural stem cells or oligodendrocyte progenitor cells (OPCs). Glioma-propagating cells (GPCs) that have stem-like properties have been derived from tumor variants such as glioblastoma multiforme (GBM) and oligodendroglial tumors, the latter being more chemosensitive with better prognosis. It has been suggested that such differences in chemosensitivity arise from the different profiles of OPCs versus neural stem cells. We thus explored if GPCs derived from these glioma variants can serve as reliable in vitro culture systems for studies. We utilized gene expression analyses, since GBM and oligodendrogliomas can be molecularly classified. Accordingly, we derived a gene signature distinguishing oligodendroglial GPCs from GBM GPCs collated from different studies, which was enriched for the Wnt, Notch and TGF-beta pathways. Using a novel method in glioma biology, the Connectivity Map, we mapped the strength of gene signature association with patient gene expression profiles in 2 independent glioma databases [GSE16011, http://caintegrator-info.nci.nih.gov/rembrandt]. Our gene signature consistently stratified survival in glioma patients. This data would suggest that in vitro low passage GPCs are similarly driven by transcriptomic changes that characterize the favorable outcome of oligodendrogliomas over GBM. Additionally, the gene signature was associated with the 1p/19q co-deletion status, the current clinical indicator of chemosensitivity. Our gene signature detects molecular heterogeneity in oligodendroglioma patients that cannot be accounted for by histology or the 1p/19q status alone, and highlights the limitation of morphology-based histological analyses in tumor classification, consequently impacting on treatment decisions.
Progenitor-like traits contribute to patient survival and prognosis in oligodendroglial tumors.
Sex, Age, Disease stage, Subject
View SamplesThis work purposed on screening candidates of key genes invovled in the production of phenylacylated flavonol-glycosides
Characterization of a recently evolved flavonol-phenylacyltransferase gene provides signatures of natural light selection in Brassicaceae.
No sample metadata fields
View SamplesPatients deficient in the guanine nucleotide exchange factor DOCK8 have decreased numbers and impaired in vitro function of T regulatory (Treg) cells and make autoantibodies, but seldom develop autoimmunity. We show that similarly, Dock8-/- mice have decreased numbers and impaired in vitrofunction of Treg cells, but do not develop autoimmunity. In contrast, mice with selective DOCK8 deficiency in Treg cells develop lymphoproliferation, autoantibodies, and gastrointestinal inflammation, despite normal percentage and in vitro function of Treg cells, suggesting that deficient T effector cell function might protect DOCK8 deficient patients from autoimmunity. We demonstrate that DOCK8 associates with STAT5 and is important for IL-2 driven STAT5 phosphorylation in Treg cells. DOCK8 localizes within the lamellar actin ring of the Treg cell immune synapse (IS). Dock8-/- Treg cells have abnormal TCR-driven actin dynamics, decreased adhesiveness, altered gene expression profile, an unstable IS with decreased recruitment of signaling molecules, and impaired transendocytosis of the co-stimulatory molecule CD86. These data suggest that DOCK8 enforces immunological tolerance by promoting IL-2 signaling, TCR-driven actin dynamics, and the IS in Treg cells. Overall design: CD4+CD25+CD39+YFP+ and CD4+CD25+CD39+YFP- Treg cells were isolated from the spleen and lymph nodes of Foxp3YFP-Cre/+/Dock8flox/flox mice. Treg cells were then cultured overnight in complete media alone or in the presence of media + anti-CD3+CD28 beads (1 bead per cell). After 16 hours, cells were harvested and the RNA was isolated. For unstimulated samples, there were 4 independent YFP- samples and 6 independent YFP+ samples. For bead stimulated samples, there were 3 independent YFP- samples and 2 YFP+ samples.
DOCK8 enforces immunological tolerance by promoting IL-2 signaling and immune synapse formation in Tregs.
Specimen part, Cell line, Treatment, Subject
View SamplesTranscriptional profiling of a DEX-inducible SNRK3.15 seedlings in the presence of ABA.
A mesoscale abscisic acid hormone interactome reveals a dynamic signaling landscape in Arabidopsis.
Age, Time
View SamplesTranscriptome levels of matched patient-derived xenograft (PDX) in vitro-in vivo models. Overall design: Comparison of gene expression levels between matched patient-derived xenograft in vitro-in vivo models.
Generation of matched patient-derived xenograft in vitro-in vivo models using 3D macroporous hydrogels for the study of liver cancer.
Specimen part, Disease, Subject
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