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SRP072073
Mus musculus
5 Downloadable Samples
Illumina HiSeq 2000
Description
Group 3 innate lymphoid cells (ILC3) are composed of NCR- and NCR+ subsets located at mucosal sites exposed to billions of commensal microbes and potentially harmful pathogens. Together with T cells, the various ILC3 subsets maintain the balance between homeostasis and immune activation. Using genetic mapping, we reveal here the existence of a new subset of NCR- ILC3 transiently expressing Ncr1 but strongly related to unlabeled NCR- ILC3, demonstrating previously unsuspected heterogeneity within the NCR- ILC3 population. Notch signaling is required for the differentiation of NCR- ILC3 into NCR+ ILC3. However, we show here that Notch signaling must be sustained for the maintenance of the NCR+ phenotype and that TGF-ß impairs the development of NCR+ ILC3. Thus, ILC3 diversity and the plasticity of the NCR- and NCR+ subsets is regulated by the balance between the opposing effects of Notch and TGF-ß signaling, maintaining homeostasis in the face of continual challenges. Overall design: Transcriptional profiling of three ILC subsets (NCR-FM-, NCR-FM- and NCR+FM+) using RNA sequencing
Publication Title
Transforming growth factor-β and Notch ligands act as opposing environmental cues in regulating the plasticity of type 3 innate lymphoid cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
CD103+CD11b+ dendritic cells (DC) are unique to the intestine, but the factors governing their differentiation are unclear. Here we show that transforming growth factor receptor 1 (TGF beta 1) has an indispensable, cell intrinsic role in the development of these cells. Deletion of Tgfbr1 results in markedly fewer intestinal CD103+CD11b+ DCs and a reciprocal increase in the CD103CD11b+ DC subset. Transcriptional profiling identifies markers that define the CD103+CD11b+ DC lineage, including CD101, TREM1 and Siglec-F, and shows that the absence of CD103+CD11b+ DCs in CD11c-Cre.Tgfbr1fl/fl mice reflects defective differentiation from CD103CD11b+ intermediaries, rather than an isolated loss of CD103 expression. The defect in CD103+CD11b+ DCs is accompanied by reduced generation of antigen-specific, inducible FoxP3+ regulatory T (Treg) cells in vitro and in vivo, and by reduced numbers of endogenous TH17 cells in the intestinal mucosa. Thus, TGF beta 1 mediated signalling may explain the tissue-specific development of these unique DCs.
Publication Title
TGFβR signalling controls CD103<sup>+</sup>CD11b<sup>+</sup> dendritic cell development in the intestine.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2000
Description
Homeostasis of the gut microbiota is pivotal to the survival of the host. Intestinal T cells and Innate Lymphoid cells (ILCs) control the composition of the microbiota and respond to its perturbations. Interleukin 22 (IL-22) plays a pivotal role in the immune control of gut commensal and pathogenic bacteria and is secreted by a heterogeneous population of intestinal T cells, NCR- ILC3 and NCR+ILC3. Expression of NCR by ILC3 is believed to define an irreversible effector ILC3 end-state fate in which these cells are key to control of bacterial infection via their production of IL-22. Here we identify the core transcriptional signature that drives the differentiation of NCR- ILC3 into NCR+ ILC3 and reveal that NCR+ILC3 exhibit more plasticity than originally thought, as NCR+ ILC3 can revert to NCR- ILC3. Contrary to the prevailing understanding of NCR+ ILC3 genesis and function, in vivo analyses of mice conditionally deleted of the key ILC3 genes Stat3, Il22, Tbet and Mcl1 demonstrated that NCR+ ILC3 were not essential for the control of colonic infections in the presence of T cells. However, NCR+ ILC3 were mandatory for homeostasis of the caecum. Our data identify that the interplay of intestinal T cells and ILC3 results in robust complementary fail-safe mechanisms that ensure gut homeostasis. Overall design: Transcriptional profiling of wild-type and T-bet knockout innate lymphoid cells (ILC3) using RNA sequencing
Publication Title
Complementarity and redundancy of IL-22-producing innate lymphoid cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Drosophila melanogaster
- 7 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
We used oligonucleotide microarrays to address the specificities of transcriptional responses of adult Drosophila to different stresses induced by paraquat and H2O2, two oxidative stressors, and by tunicamycin which induces an endoplasmic reticulum (ER) stress. Flies were tested 24 hours after exposure to continuous stresses induced by ingestion of paraquat, H2O2 or tunicamycin at concentrations leading to similar effects on viability. We used concentrations of 1% H2O2, 5mM paraquat and 12uM of tunicamycin which lead to negligeable mortality at 24 hours. A paraquat concentration of 15mM was also used for comparison with previous studies Both specific and common responses to the three stressors were observed and whole genome functional analysis identified several important classes of stress responsive genes. Within some functional classes, we observed large variabilities of transcriptional changes between isozymes, which may reflect unsuspected functional specificities.
Publication Title
Genome wide analysis of common and specific stress responses in adult drosophila melanogaster.
Sample Metadata Fields
Sex, Age, Compound, Time
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Background. Primary cilia (PC) are solitary antennae present at the cell surface. These non-motile cilia play an important role in organ development and tissue homeostasis through the transduction of the Hedgehog (Hh) signaling pathway. We recently revealed the presence of PC in the epithelium of the developing epididymis, an organ of the male reproductive system whose dysfunction triggers male infertility. Acknowledging that systemic blockade of the Hh pathway trigger epididymal dysfunctions in vivo, our main goals were 1) to portray the epididymal Hh environment, 2) to determine the direct responsiveness of epididymal epithelial cells to Hh, and 3) to define the contribution of PC to the transduction of this pathway. Results. The Hh ligands Indian and Sonic hedgehog (Ihh and Shh) were respectively located in principal and clear cells of the mouse epididymis by immunofluorescent staining. The propensity of epididymal principal cells to respond to Hh signaling was assessed on immortalized epididymal DC2 cells by western-blot, confocal imaging and 3D-reconstruction. Our results indicate that epididymal principal cells secrete Ihh and expose PC that co-localize with the conventional acetylated tubulin/Arl13b ciliary markers, as well as with GLI3 Hh signaling factor. Gene expression microarray profiling indicated that the expression of 43 and 248 genes was respectively and significantly modified following pharmacological treatment of DC2 cells with the Hh agonist SAG (250 nM) or the Hh antagonist cyclopamine (20 µM) compared with the control. Among Hh target genes identified, 6.7 % presented perfect matches for GLI-transcription factor consensus sequences, and the majority belonged to interferon-dependent immune response and lipocalin 2 pathways. Finally, the contribution of epididymal PC to the transduction of canonical Hh pathway was validated by ciliobrevinD treatment, which induced a significant decrease of PC length and the expressional reduction of Hh signalling targets. Conclusions. All together our data indicate that PC from epithelial principal cells regulate gene expression profile through a possible autocrine Hh signaling. This provides new hypotheses regarding the potential contribution of PC and Hh signaling in intercellular cross-talk and immunological regulation of the epididymis.
Publication Title
Hedgehog signaling pathway regulates gene expression profile of epididymal principal cells through the primary cilium.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 191 Downloadable Samples
- Illumina HiSeq 3000
Description
High endothelial venules (HEVs) are specialized blood vessels allowing recirculation of naïve lymphocytes through lymphoid organs. Here, using full length single-cell RNA sequencing, RNA-FISH, flow cytometry and immunohistofluorescence, we reveal the heterogeneity of HEVs in adult mouse peripheral lymph nodes (PLNs) under conditions of homeostasis, antigenic stimulation and after inhibition of lymphotoxin-b receptor (LTbR) signaling. We demonstrate that HEV endothelial cells are in an activated state during homeostasis, and we identify the genes characteristic of the differentiated HEV phenotype. We show that LTbR signaling regulates many HEV genes and pathways in resting PLNs, and that immune stimulation induces a global and temporary inflammatory phenotype in HEVs without compromising their ability to recruit naïve lymphocytes. Most importantly, we uncover differences in the regulation of genes controlling lymphocyte trafficking, Glycam1, Fut7, Gcnt1, Chst4, B3gnt3 and Ccl21a, that have implications for HEV function and regulation in health and disease. Overall design: Comparison of High Endothelial Cells and Blood Endothelial Cells from mouse lymph nodes under 4 different conditions with a total of 220 single cells.
Publication Title
Single-Cell Analysis Reveals Heterogeneity of High Endothelial Venules and Different Regulation of Genes Controlling Lymphocyte Entry to Lymph Nodes.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
We assessed the gene expression profile of purified CD205+CD8+ Dendritic Cells isolated from murine spleens.
Publication Title
NOD2 modulates immune tolerance via the GM-CSF-dependent generation of CD103<sup>+</sup> dendritic cells.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 33 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Role of Tet1/3 Genes and Chromatin Remodeling Genes in Cerebellar Circuit Formation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 33 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptome analysis of mRNA samples purified from developing cerebellar granule cells and ES cell-derived granule cells using translating ribosome affinity purification (TRAP) method.
Publication Title
Role of Tet1/3 Genes and Chromatin Remodeling Genes in Cerebellar Circuit Formation.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 16 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We collected tissues from bent cotyledon stage zygotic embryos, proliferating tissue at day 7 and day 14 induction of somatic embryogenesis and mature somatic emrbyos in a wild type (Col-0) and vtc2 (SALK_146824) insertion.
Publication Title
Vitamin C deficiency improves somatic embryo development through distinct gene regulatory networks in Arabidopsis.
Sample Metadata Fields
No sample metadata fields
View Samples