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 SamplesInnate lymphoid cells (ILC) represent innate versions of T helper and cytotoxic T cells that differentiate from committed ILC precursors (ILCP). Still, how ILCP relate to mature tissue-resident ILCs remains unclear. We observed that a population of CD117+ ILC from peripheral blood (PB) of healthy donors does not represent any conical ILC subset, but expressed marker (CD117) commonly expressed by hemato-lymphoid progenitors. We therefore hypothesized PB CD117+ ILC might include uncommitted lymphoid precursors. In order to further understand the identity of PB CD117+ ILC, we profiled the transcriptome of highly purified circulating CD117+ ILC compared to CD34+ HSC, the latter representing immature hematopoietic progenitors with multi-lineage potential. Clear differences in gene expression profiles emerged, with a large cluster of 1540 genes expressed at substantially higher levels in CD117+ ILC. In contrast, CD34+ HSC cells highly expressed genes involved in the broad development of diverse hematopoietic lineages. Compared to HSC, CD117+ ILC express high levels of TF that have been shown to be essential for murine ILC development and we did not detect transcripts characteristic of T and B cells development. Transcriptomic analysis suggested that CD117+ ILC represent lymphoid-biased progenitors carrying a TF expression profile resembling a multi-potent ILC precursor (ILCP). Overall design: CD117+ ILC and CD34+ HSC were freshly isolated by FACS of peripheral blood of two healthy adult individuals. In total, 4 samples were analyzed and comparing between two cell populations.
Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation.
Specimen part, Disease, Disease stage, Treatment, Subject
View SamplesUltra low input sequencing of FACS sorted primary murine microglia from CSF-1 or IL-34 deficient forebrain and cerebella, at P8 and 9 weeks Overall design: Csf1fl/fl vs NesCreCsf1fl/fl: 3-4 biological replicates per timepoint per group; Il34wt/wt vs Il34Lacz/Lacz: 2-3 biological replicates per timepoint per group. P8, 9weeks
CSF-1 controls cerebellar microglia and is required for motor function and social interaction.
Age, Specimen part, Subject
View SamplesLung alveolarization is a complex process that involves interactions between several cell types and leads to considerable increase in gas-exchange surface area. The step designated secondary septation includes elastogenesis from interstitial fibroblasts.
Gene expression profiling in lung fibroblasts reveals new players in alveolarization.
No sample metadata fields
View SamplesTranscript profiling analysis of Hydraulic conductivity of Root 1 (HCR1) mutant compared to wild type (Col-0) using ARABIDOPSIS GENE1.1ST ARRAY STRIP (901793, Affymetrix, Santa Clara, USA).
A Potassium-Dependent Oxygen Sensing Pathway Regulates Plant Root Hydraulics.
Age, Specimen part
View SamplesGenetic and epigenetic processes result in gene expression changes through alteration of the chromatin structure. The relative position of genes on chromosomes has therefore important functional implications and can be exploited to model microarray datasets. Gliomas are the most frequent primary brain tumours in adults and their prognosis is related to histology and grade. In oligodendrogliomas, allelic loss of 1p/19q and hypermethylation of MGMT promoter is associated with longer survival and chemosensitivity. In this work we used oligonucleotide microarray to study a group of 30 gliomas with various oligodendroglial and astrocytic components. We used an original approach combining a wavelet model of inter-probe genomic distance (CHROMOWAVE) and unsupervised method of analysis (Singular Value Decomposition) in order to discover new prognostic chromosomal patterns of gene expression. We identified a major pattern of variation that strongly correlated with survival (p= 0.007) and could be visualized as a genome-wide chromosomal pattern including widespread gene expression changes on 1p, 19q, 4, 18, 13 and 9q and multiple smaller clusters scattered along chromosomes. Gene expression changes on chromosomes 1p, 19q and 9q were significantly correlated with the allelic loss of these regions as measured by FISH. Differential expression of genes implicated in drug resistance was also a feature of this chromosomal pattern and in particular low expression of MGMT was correlated with favourable prognosis (p<0.0001). Remarkably, unsupervised analysis of the expression of individual genes and not of their chromosomal ensemble produced a pattern that could not be associated with prognosis, emphasizing the determinant role of the wavelet mathematical modelling.
Chromosomal patterns of gene expression from microarray data: methodology, validation and clinical relevance in gliomas.
No sample metadata fields
View SamplesNitric oxide and NO-derived species (RNS) are defense molecules with broad antimicrobial activity. Micro-organisms have developed strategies to sense RNS and counteract their damaging effects. We used Saccharomyces cerevisiae, harbouring a deletion of YHB1 that encodes the main NO scavenger enzyme, to study consequences of RNS exposure on whole genome transcriptional response. The expression of >700 genes was altered on RNS treatment. No major role for ROS-scavenging enzymes was found, and the respiratory chain, the main site of ROS production, had only minor involvement in the RNS-induced stress. The changes were generally transient and also found after treatment with the respiratory inhibitor myxothiazol. 117 genes however showed a persistent response which was not observed after myxothiazol treatment. Of these, genes of the glutathione and DNA repair systems, iron homeostasis and transport were found up-regulated. Severe repression of genes of respiratory chain enzymes was observed. Many of these genes are known to be regulated by the transcription factor Hap1p suggesting that RNS might interfere with Hap1p activity. We showed also that Msn2/4p and Yap1p, key regulators of the response to, respectively, general stress and oxidative stress, played a role in mediating the RNS-induced response.
Transcriptional response to nitrosative stress in Saccharomyces cerevisiae.
Compound, Time
View SamplesNMJ Junction various time points normal C57BL10 LCM mRNA
Intracellular expression profiling by laser capture microdissection: three novel components of the neuromuscular junction.
No sample metadata fields
View SamplesEffect of absence of interaction with MHC class II on memory CD4 T cells
Noncognate interaction with MHC class II molecules is essential for maintenance of T cell metabolism to establish optimal memory CD4 T cell function.
Sex, Specimen part
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