Treatment of severely refractory Crohns disease (CD) patients remains a clinical challenge. Recent studies show efficacy of autologous hematopoietic stem cell transplant (HSCT) in these severely compromised patients. HSCT is thought to eliminate auto-reactive cells; however the mechanisms are incompletely understood. We followed a group of patients (n=18) receiving autologous HSCT, with 50% of them achieving endoscopic drug-free remission. To elucidate the mechanism driving efficacy we compared the immunological changes induced by HSCT in responders and non-responders.
Differences in peripheral and tissue immune cell populations following hematopoietic stem cell transplantation in Crohn's disease patients.
Sex, Age, Specimen part, Disease, Time
View SamplesTreatment of severely refractory Crohn's disease (CD) patients remains a clinical challenge. Recent studies show the efficacy of autologous hematopoietic stem cell transplant (HSCT) in these severely compromised patients. HSCT is thought to eliminate auto-reactive cells; however, no specific studies of immune reconstitution in CD patients are available. We studied a group of CD patients receiving autologous HSCT, with 50% of them achieving endoscopic drug-free remission. To elucidate the mechanism driving efficacy, we studied changes in the immune cell composition in tissue induced by HSCT. Overall design: Biopsy mRNA profiles of 14 CD patients undergoing HSCT were generated by deep sequencing, using HiSeq-4000 platform (Illumina, San Diego, CA).
Differences in Peripheral and Tissue Immune Cell Populations Following Haematopoietic Stem Cell Transplantation in Crohn's Disease Patients.
Sex, Specimen part, Disease, Subject
View SamplesWe used RNA sequencing to study gene expression in lymph node derived DCs from anaphylactic mice sensitized intranasally with the major peach allergen Pru p 3, during the acute reaction phase, induced intraperitoneally. In total, 237 genes changed significantly, 181 showing at least two-fold changes. Almost three quarters of these increased during anaphylaxis Overall design: 5 Female Balb/c mice aged 4-5 weeks, were sensitized to peach using intranasally administered Pru p 3 in combination with LPS and challenged intraperitoneally as described previously . 5 Littermates, treated with intranasally administered PBS (instead of Pru p 3 and LPS), and later given an intraperitoneal challenge as per the anaphylactic mice, were used for comparison.
Transcriptional Profiling of Dendritic Cells in a Mouse Model of Food-Antigen-Induced Anaphylaxis Reveals the Upregulation of Multiple Immune-Related Pathways.
Sex, Cell line, Treatment, Subject
View SamplesCurrent pipelines used to map genetrap insertion sites are based on inverse- or splinkerette-PCR methods, which despite their efficacy are prone to artifacts and do not provide information on the impact of the genetrap on the expression of the targeted gene. We developed a new method, which we named TrapSeq, for the mapping of genetrap insertions based on paired-end RNA sequencing. By recognizing chimeric mRNAs containing genetrap sequences spliced to an endogenous exon, our method identifies insertions that lead to productive trapping. Overall design: We conducted two independent screenings for sensitivity against 6-thioguanine (6TG) and an ATR inhibitor (ATRi). We applied our RNAseq-based pipeline (TrapSeq) to identify mutations that provide resistance to these reagents. Importantly, and besides its use for screenings, when applied to individual clones our method provides a fast and cost-effective way that not only identifies the insertion site of the genetrap but also reveals the impact of the insertion on the expression of the trapped gene. Please note that HAP1, haploid for all chromosomes, derives from near-haploid KBM7 parent line which was in turn obtained from a chronic myeloid leukemia patient in blast crisis phase (Carette et al. Nature 477:340-343, 2011).
Trap<sup>Seq</sup>: An RNA Sequencing-Based Pipeline for the Identification of Gene-Trap Insertions in Mammalian Cells.
Specimen part, Cell line, Subject
View SamplesSASL1 is highly metastatic to lymph nodes. ACC2 is not metastatic. We compared gene expression on cultured cells to identify genes associated to metastatic spread patterns.
Premetastatic vasculogenesis in oral squamous cell carcinoma xenograft-draining lymph nodes.
Specimen part, Cell line
View SamplesDietary intervention constitutes a feasible approach for modulating metabolism and improving healthspan and lifespan. Methionine restriction (MR) delays the appearance of age-related diseases and increases longevity in normal mice. However, the effect of MR on premature aging remains to be elucidated. Here, we describe that MR extends lifespan in two different mouse models of Hutchinson-Gilford progeria syndrome (HGPS) by reversing the transcriptome alterations in inflammation and DNA-damage response genes present in this condition. Further, MR improves the lipid profile and alters the levels of bile acids, both in wild-type and in progeroid mice. Notably, treatment with the bile acid cholic acid improves healthspan and lifespan in vivo. These results suggest the existence of a metabolic pathway involved in the longevity extension achieved by MR and support the possibility of dietary interventions for treating progeria.
Methionine Restriction Extends Lifespan in Progeroid Mice and Alters Lipid and Bile Acid Metabolism.
Sex, Age, Specimen part
View SamplesNeural crest cells are a transient embryonic population, hence are neither present after bith and nor are they readily accesible for analysis. Therefore, little is known about the genetic networks that regulate NC especification, delamitation and migration from the dorsal neural tube to their final destination along the embryo.
Delamination of neural crest cells requires transient and reversible Wnt inhibition mediated by Dact1/2.
Specimen part
View SamplesWe identified fibro-inflammatory and keratin gene expression signatures in systemic sclerosis skin.
Dissecting the heterogeneity of skin gene expression patterns in systemic sclerosis.
Age, Specimen part, Race, Subject, Time
View SamplesWe identified eighty two skin transcripts significantly correlated with the severity of interstitial lung disease (ILD) in systemic sclerosis.
Skin gene expression correlates of severity of interstitial lung disease in systemic sclerosis.
Age, Specimen part, Race, Subject
View SamplesBrassinosteroids (BRs) are growth-promoting plant hormones that play a role in abiotic stress responses, but molecular modes that enable this activity remain largely unknown. Here we show that BRs participate in the regulation of freezing tolerance. BR signaling-defective mutants of Arabidopsis thaliana were hypersensitive to freezing before and after cold acclimation. The constitutive activation of BR signaling, in contrast, enhanced freezing resistance. Evidence is provided that the BR-controlled basic helixloophelix transcription factor CESTA (CES) can contribute to the constitutive expression of the C-REPEAT/DEHYDRATION-RESPONSIVE ELEMENT BINDING FACTOR (CBF) transcriptional regulators that control cold responsive (COR) gene expression. In addition, CBF-independent classes of BR-regulated COR genes are identified that are regulated in a BR- and CES-dependent manner during cold acclimation. A model is presented in which BRs govern different cold-responsive transcriptional cascades through the posttranslational modification of CES and redundantly acting factors. This contributes to the basal resistance against freezing stress, but also to the further improvement of this resistance through cold acclimation.
Brassinosteroids participate in the control of basal and acquired freezing tolerance of plants.
Age, Specimen part, Treatment
View Samples