Blimp-1 expression in T cells extinguishes the T follicular helper cell fate and drives terminal differentiation, but also limits autoimmunity. Although various factors have been described to control Blimp-1 expression in T cells, little is known about what regulates Blimp-1 expression in Th2 cells and the molecular basis of its actions. Herein, we report that STAT3 unexpectedly played a critical role in regulating Blimp-1 in Th2 cells. Furthermore, we found that the cytokine IL-10 acted directly on Th2 cells and was necessary and sufficient to induce optimal Blimp-1 expression through STAT3. Together, Blimp-1 and STAT3 amplified IL-10 production in Th2 cells, creating a strong autoregulatory loop that enhanced Blimp-1 expression. Increased Blimp-1 in T cells antagonized STAT5-regulated cell cycle and anti-apoptotic genes to limit cell expansion. These data elucidate the signals required for Blimp-1 expression in Th2 cells and reveal an unexpected mechanism of action of IL-10 in T cells, providing insights into the molecular underpinning by which Blimp-1 constrains T cell expansion to limit autoimmunity. Overall design: RNAseq of activated undifferentiated CD4 T cells with or without exogenous expression of Blimp-1.
IL-10 induces a STAT3-dependent autoregulatory loop in T<sub>H</sub>2 cells that promotes Blimp-1 restriction of cell expansion via antagonism of STAT5 target genes.
Specimen part, Subject
View SamplesThe colonic lamina propria contains a distinct population of Foxp3+ T regulatory cells (Tregs) that modulate responses to commensal microbes. Analysis of gene expression revealed that the transcriptome of colonic Tregs is distinct from splenic and other tissue Tregs. Ror and Helios in colonic Tregs mark distinct populations: Ror+Helios- or Ror-Helios+ Tregs. We uncovered an unanticipated role for Ror, a transcription factor generally considered to be antagonistic to Foxp3. Ror in colonic Tregs accounts for a small but specific part of the colon-specific Treg signature.
MUCOSAL IMMUNOLOGY. Individual intestinal symbionts induce a distinct population of RORγ⁺ regulatory T cells.
Sex, Age
View SamplesTo identify novel PPARalpha target genes involved in lipid metabolism
Evolutionarily conserved gene family important for fat storage.
No sample metadata fields
View SamplesWe performed morphogen-directed differentiation of human PSCs into HE followed by combinatorial screening of 26 candidate HSC-specifying TFs for the potential to promote hematopoietic engraftment in irradiated immune deficient murine hosts. We recovered seven TFs (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1, SPI1) that together were sufficient to convert HE into hematopoietic stem and progenitor cells (HSPCs) that engraft primary and secondary murine recipients Overall design: Examination of expression pattern in hematopoietic cells.
Haematopoietic stem and progenitor cells from human pluripotent stem cells.
Specimen part, Subject
View SamplesObjective: Long non-coding RNAs (lncRNA) regulate gene transcription and diverse cellular functions. We previously defined a novel core inflammatory and metabolic ileal gene signature in treatment naïve pediatric Crohn Disease (CD), however, genome-wide characterization of lncRNA expression was lacking. We now extend our analyses to define a more comprehensive view that includes lncRNA. Design: Using RNAseq, we performed a systematic profiling of lncRNAs and protein-coding genes expression in 177 ileal biopsies. Co-expression analysis was used to identify functions and tissue-specific expression. RT-PCR was used to test lncRNAs regulation by IL-1ß in Caco-2 enterocytes model. Results: We characterize a widespread dysregulation of 459 lncRNA in the ileum of treatment naïve pediatric CD patients. Unsupervised and supervised classifications using the 459 lncRNA showed comparable patients' grouping as the 2160 dysregulated protein-coding genes, linking lncRNA to CD pathogenesis. Co-expression and functional annotation enrichment analyses across several tissues and cell types showed that the up-regulated LINC01272 is associated with a myeloid pro-inflammatory signature while the down-regulated HNF4A-AS1 exhibits association with an epithelial metabolic signature. We further validated expression and regulation of prioritized lncRNA upon IL-1ß exposure in differentiated Caco-2 cells. Finally, we identified significant correlations between LINC01272 and HNF4A-AS1 expression and more severe mucosal injury. Conclusion: We define differentially expressed lncRNA in the ileum of treatment naive pediatric CD. We show lncRNA utility to correctly classify disease or healthy states and demonstrate their regulation in response to an inflammatory signal. These lncRNA, after mechanistic exploration, may serve as potential new targets for RNA-based interventions. Overall design: Using RNAseq, we performed a systematic profiling of lncRNAs and protein-coding genes expression in 21 days differentiated caco-2 cells
Long ncRNA Landscape in the Ileum of Treatment-Naive Early-Onset Crohn Disease.
Specimen part, Subject
View SamplesIn this study, zebrafish ZF4 and PAC2 cells were seeded in 0.5% or 1% FCS, respectively, and grown to 85% confluence and subsequently cultured for 24 hours without serum. Then they were treated with either medium without serum or medium with serum (ZF4 in 10% FCS and PAC2 in 15% FCS).After 6 hours, RNA was extracted from the cells and analyzed using the Affymetrix GeneChip Zebrafish Genome Array (GeneChip 430). There are 15502 oligonucleotide sets on each Affymetrix chip, 14895 of which can be linked to a UniGene assignment (Unigene data set 06-12-2005).
Genetic and transcriptome characterization of model zebrafish cell lines.
Cell line, Compound
View SamplesWe purified by magnet assisted cell sorting microglial cells from brains of adult Rab7 null mutant, aged mice and respective controls, isolated total RNA and performed RNAseq to determine the transciptome profiles. Overall design: Examination of transcriptomes of Rab7 null mutants and control (2 replicates each) and aged mice and young controls (3 replicates each)
Age-related myelin degradation burdens the clearance function of microglia during aging.
Age, Specimen part, Cell line, Subject
View Samplesexpression analysis from a genetically engineered mouse model of osteosarcoma
Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease.
No sample metadata fields
View SamplesGoals of this study were to identify new candidates involved in the development of the Atrioventricular cushions in the mouse heart.
Cartilage link protein 1 (Crtl1), an extracellular matrix component playing an important role in heart development.
No sample metadata fields
View SamplesComparison between ex vivo immature, mature and stimulated T cells and in vitro generated counterparts. The T cells generated in vitro were cultured on OP9-DL1 stroma supplied with growth factors.
In vitro generation of mature, naive antigen-specific CD8(+) T cells with a single T-cell receptor by agonist selection.
Specimen part
View Samples