Pmr1 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.
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View Samples5069 transcriptomes of single oligodendrocyte cells from spinal cord, substantia nigra-ventral tegmental area, striatum, amygdala, hypothalamic nuclei, zona incerta, hippocampus, and somatosensory cortex of male and female mice between post-natal day 21 and 90. The study aimed at identifying diverse populations of oligodendrocytes, and revealing dynamics of oligodendrocyte maturation. Overall design: 5069 individual cells were sampled from CNS regions of mice of various strains as detailed in the protocols section
Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system.
Sex, Cell line, Treatment, Subject
View SamplesUsing EphB2 or the ISC marker Lgr5, we have FACS-purified and profiled intestinal stem cells (ISCs), crypt proliferative progenitors and late transient amplifying cells to define a gene expression program specific for normal ISCs.
The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse.
Specimen part
View SamplesIL-22 acts on epithelial cells and has been shown to induce tissue protective and wound healing responses in these cells. But it has recently been decribed that IL-22 exacerbates ileatis after infection with T. gondii.
Interleukin-22 induces interleukin-18 expression from epithelial cells during intestinal infection.
Specimen part, Time
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 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 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 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 SamplesLymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes.
Infrequent loss of luminal differentiation in ductal breast cancer metastasis.
Specimen part
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