Breast cancer cells facilitate distant metastasis through the induction of immunosuppressive regulatory B cells, designated tBregs. We report here that, to do this, breast cancer cells produce metabolites of the 5-lipoxygenase (5-LO) pathway such as leukotriene B4 (LTB4) to activate the proliferator-activated receptor alpha (PPARalpha) in B cells. Inactivation of LTB4 signaling or genetic deficiency of PPARalpha in B cells blocks the generation of tBregs and thereby abrogates lung metastasis in mice with established breast cancer. Thus, in addition to eliciting fatty acid oxidation and metabolic signals, PPARalpha initiates programs required for differentiation of tBregs. We propose that PPARalpha in B cells or/and tumor 5-LO pathways represents new targets for pharmacological control of tBreg-mediated cancer escape.
Cancer-produced metabolites of 5-lipoxygenase induce tumor-evoked regulatory B cells via peroxisome proliferator-activated receptor α.
Specimen part
View SamplesAim: to perform a genome-wide investigation of chromatin landscape and gene expression patterns downstream of calcium and kinase signaling in Jurkat T cells. Methods: PMA and ionomycin were used to activate the calcium and kinase signalling networks involved in T cell activation. Global gene expression was measured using RNA-seq, whilst ATAC-seq was used to probe chromatin landscape following 3 hours of stimulation with PMA, ionomycin or both. All experiments were performed in triplicate. For RNA-seq all sequencing was performed using paired-end sequencing on an Illumina HiSeq2500 instrument. For ATAC-seq sequencing was performed using a HiSeq 1500. Results: we mapped approximately 60 million reads per sample for ATAC-seq, and 22 million reads per library for RNA-seq. Overall we identified 57,825 transcripts and 19,763 ATAC-seq peaks. We identifiead 1648 genes whose expression was increased by 2-fold or more by at least one treatment in comparison to untreated cells. Similarly, we identified 3972 ATAC peaks that were induced by at least 2-fold by treatment in comparison to untreated cells. Conclusions: we found that chromatin landscape was associated with gene expression downstream of calcium and kinase signaling in Jurkat cells. Further to this we found that activation of the full complement of TCR-responsive genes is dependent upon both PMA and ionomycin, and amounts to more than just the sum of both. Overall design: RNA-sequencing and ATAC-sequencing were performed after 3 hours of treatment with either PMA, ionomycin or co-treatment with PMA and ionomycin.
Integration of Kinase and Calcium Signaling at the Level of Chromatin Underlies Inducible Gene Activation in T Cells.
No sample metadata fields
View SamplesFusarium Head Blight susceptible barley variety, Morex, was infected with deoxynivalenol production deficient mutant strain (GZT40) and wild type stains (Z3639) of Fusarium graminearum. The RNA was sampled at 48 and 96 hours after inoculation. and was used hybridize to Barley_1 GeneChip. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Jayanand Boddu. The equivalent experiment is BB52 at PLEXdb.]
Transcriptome analysis of trichothecene-induced gene expression in barley.
Specimen part
View SamplesTranscriptome changes 1h or 4h following DELLA stabilisation in microdissected fully proliferating Arabidopsis leaves
Gibberellins and DELLAs: central nodes in growth regulatory networks.
Specimen part, Treatment, Time
View SamplesBarley cv. Morex inoculated with Fusarium graminearum (isolate Butte 86) or water (mock). Sampled at 24, 48, 72, 96 and 144 hours after treatment. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Jayanand Boddu. The equivalent experiment is BB9 at PLEXdb.]
Transcriptome analysis of the barley-Fusarium graminearum interaction.
Specimen part, Time
View Samples16 replication error proficient (RER-/MSI-) and 14 replication error deficient (RER+/MSI+) colorectal cancer cell lines
Replication error deficient and proficient colorectal cancer gene expression differences caused by 3'UTR polyT sequence deletions.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Renal stromal miRNAs are required for normal nephrogenesis and glomerular mesangial survival.
Specimen part
View SamplesPurpose: The goal of this study is to compare the differential expression of transcripts in control kidneys compared to kidneys lacking the miR-17~92 cluster in nephron progenitors and their derivatives by RNA-seq to identify potential miRNA targets in the mutant kidneys. Overall design: mRNA profiles of control and mutant (=Six2-TGC; miR-17~92 flx/flx) embryonic day 16 kidneys were generated by deep sequencing, in triplicate, using Illumina HiSeq2000
MicroRNA-17~92 is required for nephrogenesis and renal function.
No sample metadata fields
View SamplesThe oviducts play a critical role in gamete and embryo transport, as well as supporting fertilization and early embryo development. Progesterone receptor (PGR) is a transcription factor highly expressed in oviductal cells, while its activating ligand, progesterone (P4), surges to peak levels as ovulation approaches. P4 is known to regulate oviduct cilia beating and muscular contractions in vitro, but how PGR may mediate this in vivo is poorly understood. We used PGR-knockout (PRKO) mice to determine how PGR regulates oviductal function during the periovulatory period, in particular oviductal transport and embryo support.
Progesterone receptor-dependent regulation of genes in the oviducts of female mice.
Specimen part
View SamplesRPS19 mutations are the most common cause of the human disorder Diamond Blackfan Anemia. The R62W mutation was hypothesized to act in a dominant negative fashion and mice expressing RPS19R62W have many of the characteristics of Diamond Blackfan Anemia.
A transgenic mouse model demonstrates a dominant negative effect of a point mutation in the RPS19 gene associated with Diamond-Blackfan anemia.
Specimen part
View Samples