TCERG1 is a highly conserved human protein implicated in interactions with the transcriptional and splicing machinery. To investigate TCERG1 function, we survey genome-wide changes in transcript and exon levels upon TCERG1 knockdown in HEK293T cells. Our data revealed that TCERG1 regulates different types of alternative spliced events, indicating a broad role in the regulation of alternative splicing.
Transcriptional Elongation Regulator 1 Affects Transcription and Splicing of Genes Associated with Cellular Morphology and Cytoskeleton Dynamics and Is Required for Neurite Outgrowth in Neuroblastoma Cells and Primary Neuronal Cultures.
Cell line
View SamplesSenescent cells accumulate in many ageing-associated diseases such as pulmonary fibrosis, and targeting these cells has recently emerged as a promising therapeutic approach. Here, we take advantage of the high ß-galactosidase activity of senescent cells to design a targeted drug delivery system based on the encapsulation of drugs with galacto-oligosaccharides (GalNP beads). In this experiment we show that gal-encapsulated rhodamine target senescent cells in the context of pulmonary fibrosis in mice. Overall design: 8- to 10-week-old C57BL/6 wild-type mice were intratracheally inoculated with bleomycin at 1.5 U/kg of body weight. Two weeks later mice were i.v. injected with 200 µl of a solution of GalNP beads loaded with rhodamine [GalNP(rho)] at 4 mg/ml, equivalent to 1 mg/kg of deliverable rhodamine. 6 hours later mice were sacrificed and lung cells were analysed by flow cytometry and sorted into Rho+ or Rho- cells, all CD45-CD31-.
A versatile drug delivery system targeting senescent cells.
Specimen part, Cell line, Subject
View SamplesSenescence is a cellular phenotype present in health and disease, characterized by a stable cell cycle arrest and an inflammatory response, denominated senescence-associated secretory phenotype (SASP). The SASP is important in influencing the behaviour of neighbouring cells and altering the microenvironment; yet, this role has been mainly attributed to soluble factors. Here, we show that both the soluble factors in addition to small extracellular vesicles (sEV) are capable of transmitting paracrine senescence to nearby cells. Analysis of individual cells internalizing sEV, using a Cre-reporter system, show a positive correlation between sEV uptake and senescence activation. Interestingly, we find an increase in the number of multivesicular bodies during senescence in vivo. sEV protein characterization by mass spectrometry (MS) followed by a functional siRNA screen identify the Interferon Induced Transmembrane Protein 3 (IFITM3) as partially responsible for transmitting senescence to normal cells. Altogether, we found that sEV contribute to paracrine senescence. Overall design: SASP related mRNA transcripts in HFFF2 treated with sEV from iRAS cells in comparison with HFFF2 treated with sEV from iC cells
Small Extracellular Vesicles Are Key Regulators of Non-cell Autonomous Intercellular Communication in Senescence via the Interferon Protein IFITM3.
Disease, Subject
View SamplesYerba mate (YM) has been shown to have anti-inflammatory properties in several studies. However, this effect has been found mainly in obesity-related in inflammation. The aim of this work was to study the effect of YM in cultured peripheral blood mononuclear cells to see whether it has anti-inflammatory properties. We stimulated peripheral blood mononuclear cells in vitro with phitohemaglutinin in the presence of yerba mate and determined their activation measuring the the expression of CD25 by flow cytometry. We observed that YM treatment produced a dose-dependent reduction in PBMC activation (CD25 positive cells) when they were stimulated with PHA. This effect was also observed in T cells (CD3 positive) subpopulation. Microarray analysis revealed the differential expression of 128 genes in YM-treated cells. According to a protein-protein interaction database, these genes were highly connected and they are involved in inflammatory response. In summary, it was demonstrated that YM produces a reduction in the amount of activated cells under the stimulation of PHA. Therefore, it might be used in diseases with an inflammatory component.
Yerba mate (Ilex paraguariensis) inhibits lymphocyte activation in vitro.
Sex, Specimen part
View SamplesPmr1 is a cis-Golgi Mn/Ca transporter with a key role in protein glycosylation and manganese detoxification.
Manganese redistribution by calcium-stimulated vesicle trafficking bypasses the need for P-type ATPase function.
No sample metadata fields
View SamplesHow chromatin controls transcription elongation and splicing is an open question. Here we determine the transcriptomic changes of cells partially depleted of core histones. For that we construct a cell line with Doxycycline-controlled levels of the histone regulatory protein SLBP (HCT-shSLBP). HCT-shSLBP is derived from the human colon cancer cell line HCT116.
Defective histone supply causes changes in RNA polymerase II elongation rate and cotranscriptional pre-mRNA splicing.
Specimen part, Cell line
View SamplesGlycolytic Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyzes the conversion of glyceraldehyde 3-phospate to 1,3-bisphosphoglycerate by coupling with the reduction of NAD+ to NADH. We generated mutants of the Arabidopsis plastidial GAPDH isoforms (At1g79530, At1g16300; GAPCp1, GAPCp2). gapcp double mutants (gapcp1 gapcp2) display a drastic phenotype of arrested root development and sterility.Complex interactions occurring between ABA and sugar signal transduction pathways have been shown, but the molecular mechanisms connecting both pathways are not well understood. Since we found drastic carbohydrate changes in gapcp1 gapcp2, we studied their response to ABA. by performing a microarray analysis comparing gapcp1 gapcp2 and wild type seedlings after a long term treatment with ABA.
Arabidopsis plants deficient in plastidial glyceraldehyde-3-phosphate dehydrogenase show alterations in abscisic acid (ABA) signal transduction: interaction between ABA and primary metabolism.
Specimen part, Treatment
View SamplesWhe embryonic stem cells are in vitro expanded threir telomereres lengthen, in the absence of genetic manipulations, concomitant with the loss of heterochromatic marks. In order to analyze whether there would be changes in gene expression during in vitro expansion we performed RNA-seq and found no substantial differences in gene expression at passage 6 or 16. Overall design: Embryonic stem (ES) cells were derived from blastocysts expressing GFP in the Rosa26 locus. Four independent lines of ES were in vitro expanded to passage 16. Total RNA was extracted from each independent clones, RNA was extracted and prepared for RNA-seq.
Generation of mice with longer and better preserved telomeres in the absence of genetic manipulations.
Specimen part, Cell line, Treatment, Subject
View SamplesAlthough Human papillomavirus infection is the main causal factor for cervical cancer (CC), there is data suggesting genetic factors could modulate the risk and progression of CC. Sibling studies suggest that maternally inherited factors could be involved in CC. To assess whether mitochondrial DNA (mtDNA) polymorphisms are associated to cervical cancer, HPV infection and HPV types, a case-control study was performed in the Mexican mestizo population. The polymorphism of mtDNA D-Loop was investigated in 187 cervical cancer patients and 270 healthy controls. D-loop was amplified from a blood DNA sample and analyzed by sequencing. HPV was detected and typed in cervical scrapes from both groups. mtDNA polymorphisms were compared in the whole samples and stratified by HPV types. The expression of 29 mitochondrial genes was analyzed in a subset of 45 tumor biopsies using the expression microarray ST1.0. The Amerindian haplogroup B2 increased the risk for CC (OR=1.6, 95% CI: 1.05-2.58) and showed an additive effect of 36% over the risk conferred by the HPV (OR=153, 95% CI: 65.4-357.5). The frequency of HPV 16, 18, 31 and 45 in cancer samples was similar in all haplogroups but one (D1). It showed a very low frequency of HPV16, any HPV18 and high frequency of HPVs 31, 45 and other types. Two mtDNA genes (MT-TD, MTTK) could be involved in the increased risk conferred by the haplogroup B2, since they were up-regulated exclusively in B2 tumors (p<0.05, t-test). These findings will contribute to clarify the importance of genetic factors in CC.
The Amerindian mtDNA haplogroup B2 enhances the risk of HPV for cervical cancer: de-regulation of mitochondrial genes may be involved.
Specimen part
View SamplesWhole-genome expression of peripheral blood leukocytes was measured in 22 patients and 24 controls using the Human Gene 1.0 ST array by Affymetrix
Transcriptomic profile reveals gender-specific molecular mechanisms driving multiple sclerosis progression.
Sex, Age, Specimen part, Disease
View Samples