S-adenosylmethionine (SAM) is the methyl donor for biological methylation modifications that regulate protein and nucleic acid functions. Here we show that methylation of a phospholipid, phosphatidylethanolamine (PE), is the major consumer of SAM in budding yeast. The induction of phospholipid biosynthetic genes is accompanied by induction of the enzyme that hydrolyzes S-adenosylhomocysteine (SAH), a product and inhibitor of methyltransferases. Beyond its function for the synthesis of phosphatidylcholine (PC), the methylation of PE facilitates the turnover of SAM for the synthesis of cysteine and glutathione. Strikingly, cells that lack PE methylation accumulate SAM, which leads to hypermethylation of histones and the major phosphatase PP2A, dependency on cysteine, and sensitivity to oxidative stress. Without PE methylation, particular sites on histones then become methyl sinks to enable the turnover of SAM. These findings reveal an unforeseen metabolic function for phospholipid and histone methylation intrinsic to the life of a cell. Overall design: Two biological replicates of wild type and cho2? cells in YPL media, in SL media after 1 hour and in SL media after 3 hour were collected for sequencing.
A Metabolic Function for Phospholipid and Histone Methylation.
Cell line, Subject, Time
View SamplesHow secondary CD4 T cell effectors, derived from resting memory cells, differ from primary cells, derived from nave precursors, and how such differences impact recall responses to pathogens is unknown.
Memory CD4+ T-cell-mediated protection depends on secondary effectors that are distinct from and superior to primary effectors.
Specimen part
View SamplesWe report RNA sequencing of single olfactory neurons from mouse olfactory epithelium in developmental progression from progenitors to precursors to immature neurons to mature neurons. Most mature neurons expressed only one of ~ 1000 odorant receptor genes (Olfrs) at high levels, whereas many immature neurons expressed low levels of multiple Olfrs. Overall design: Investigating expression of odorant receptors genes in mouse olfactory sensory neurons during development.
Single-cell transcriptomics reveals receptor transformations during olfactory neurogenesis.
Cell line, Subject
View SamplesTGF is one of most intensively studied regulators of extracellular matrix formation, and has been implicated in the development of pulmonary fibrosis in different models. However, little is know about the role of miRNAs in TGF mediated fibrogenic gene regulation. By using miRNA qRT-PCR array, we have identified miRNAs whose expression are regulated by TGF in IMR-90 cells. Among those down-regulated miRNAs are miR-29 family members. Knockdown miR-29 in IMR-90 cells results in up-regulation of a large number of extracellular matrix and fibrogenic genes including family members of collagen, laminin, integrin, ADAM and MMP, many of them are predicted or confirmed miR-29 targets. Hierarchichal clustering analysis of mRNA array data revealed that many extracellular matrix and fibrogenic genes up-regulated by TGF in IMR-90 cells, are also up-regulated in miR-29 KD cells. Moreover, the similar set of extracellular matrix and fibrogenic genes is also significantly up-regulated in bleomycin treated mouse lungs. Together, our data strongly suggest that downstream of the TGF, miR-29 is a master modulator of genes involved in extracellular matrix formation and might play a significant role in pulmonary fibrosis.
miR-29 is a major regulator of genes associated with pulmonary fibrosis.
Specimen part, Cell line
View SamplesGW182 (Tnrc6a) is a key component of RISC (miRNA-Induced Silencing Complex) that plays a critical role in miRNA-mediated gene silencing. Here, we show that GW182 is expressed in the yolk sac endoderm, and that gene-trap disruption of GW182 leads to growth arrest of yolk sac endoderm, impaired hematopoiesis and embryonic lethality.
Trinucleotide repeat containing 6a (Tnrc6a)-mediated microRNA function is required for development of yolk sac endoderm.
Specimen part
View SamplesHow IL-2 produced by secondary CD4 T cell effectors, derived from resting memory cells, impacts memory CD4 T cell function and survival to memory following antigen re-encounter is unknown.
Effector CD4 T-cell transition to memory requires late cognate interactions that induce autocrine IL-2.
Treatment, Time
View SamplesThis study aimed at exploring the physiological function of mammalian HYPB by means of knockout mouse model. Homogenous disruption of mouse Hypb gene leads to embryonic lethality at E10.5-E11.5. Severe vascular defects were observed in the Hypb-/- embryos, yolk sac and placenta.In the mutant embryo and yolk sac, disorganized and abnormally dilated capillaries cannot be remodeled into large blood vessels or intricate networks. Thus, our results suggest that the mammalian HYPB HMT plays an important role in embryonic vascularization.
Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling.
No sample metadata fields
View SamplesCD4 T cells can differentiate into a hetergenous population of effector T cells. A population of cytotoxic CD4 T cells can be generated against influenza challenge, however identifying these cells have been challenging. The expression of NKG2A/C/E on CD4 T cells identifies CD4 T cells with cytotoxic potential thus allowing further characterization of this subset of CD4 effector cells.
NKG2C/E Marks the Unique Cytotoxic CD4 T Cell Subset, ThCTL, Generated by Influenza Infection.
Specimen part
View SamplesHypertrophic scar (HTS) formation is characterized by exuberant fibroproliferation for reasons that remain poorly understood1. One important but often overlooked component of wound repair is mechanical force, which regulates reciprocal cell-matrix interactions through focal adhesion components including focal adhesion kinase (FAK)1,2. Here we report that FAK is activated following cutaneous injury and that this activation is potentiated by mechanical loading. Transgenic mice lacking fibroblast-specific FAK exhibit significantly less fibrosis in a preclinical model of HTS formation. Inflammatory pathways involving monocyte chemoattractant protein-1 (MCP-1), a chemokine highly implicated in human skin fibrosis3, are triggered following FAK activation, mechanistically linking physical force to fibrosis. Further, small molecule inhibition of FAK effectively abrogates fibroproliferative mechanisms in human cells and significantly reduces scar formation in vivo. Collectively, these findings establish a molecular basis for HTS formation based on the mechanical activation of fibroblast-specific FAK and demonstrate the therapeutic potential of targeted mechanomodulatory strategies.
Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling.
Sex, Specimen part
View SamplesHuman mesenchymal stem cells (hMSCs) were transduced using lentivirus containing the the triple fusion reporter gene fluc-mrfp-ttk. Microarray studies of hMSCs after transduction with the triple reporter genes using lentivirus were performed to study the effects of transduction on stem cell properties using an oligonucleotide human microarray. Transduced cells were sorted by FACS. Cells with high and low signals were ftacrtionated, and gene expression profiles were determined.
Transcriptional profiling of human mesenchymal stem cells transduced with reporter genes for imaging.
No sample metadata fields
View Samples