Radial progenitors deficient in both Mek1 and Mek2 fail to transition to the gliogenic mode in late embryogenesis, and astrocyte and oligodendroglial precursors fail to appear. In exploring mechanisms, we found the Ets transcription family member Etv5/Erm is strongly regulated by MEK. Our microarray assay showed that Erm is specifically downregulated in Mek mutant brain.
MEK Is a Key Regulator of Gliogenesis in the Developing Brain.
Specimen part
View SamplesInactivation of ERK/MAPK signaling in developing postmitotic cortical excitatory neurons results in a significent loss of Ctip2 positive layer 5 neurons and axon projections. Microarray dada revealed the reduced levels of a vast majority of layer V specific transcripts.
Layer specific and general requirements for ERK/MAPK signaling in the developing neocortex.
Specimen part
View SamplesAffymetrix human whole transcriptome array (HTA 2.0) completed on patients with Crohn's disease undergoing their first ileocolic resection
Predicting Risk of Postoperative Disease Recurrence in Crohn's Disease: Patients With Indolent Crohn's Disease Have Distinct Whole Transcriptome Profiles at the Time of First Surgery.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Evidence for multiple roles for grainyhead-like 2 in the establishment and maintenance of human mucociliary airway epithelium.[corrected].
Specimen part, Treatment
View SamplesThe airways of the human lung are lined by an epithelium made up of ciliated and secretory luminal cells and undifferentiated p63+ Krt5+ basal cells. The integrity of this epithelium and its ability to act as a selective barrier are critical for normal lung function. In other epithelia there is evidence that transcription factors of the evolutionarily conserved grainyheadlike (GRHL) family play key roles in co-ordinating the expression of numerous proteins required for epithelial morphogenesis, differentiation, remodeling and repair. However, little is known about their function in the adult lung. Here, we focus on the role of GRHL2 in primary human bronchial epithelial (HBE) cells, using either shRNA or a dominant negative protein (DN-GRHL2) to inhibit its function. We follow changes in epithelial phenotype, and in gene transcription using RNA-seq or microarray analysis, both in undifferentiated basal cells and in cells differentiating in air-liquid interface culture into a mucociliary epithelium with transepithelial electrical resistance. We identify several hundreds of genes that are directly or indirectly regulated by GRHL2. Using ChIP-seq to map sites of GRHL2 binding in the basal cells we identify 7,687 potential primary targets, and confirm that GRHL2 binding is strongly enriched near GRHL-regulated genes. Different subsets of the large cohort of potential GRHL2 targets appear to be active in basal and differentiated cells. Taken together, the results strongly support the hypothesis that GRHL2 plays a key role in regulating many physiological functions of human airway epithelium, including those involving cell adhesion, polarity and morphogenesis. Overall design: Frozen primary human bronchial epithelial (HBE) cells were obtained from three donors. Passage 2 cells at 40% confluence were infected with H2B-GFP or DN-GRHL2 lentivirus and 1 mg/ml puromycin added 48 h later. At confluence, Doxycycline 0.5 mg/ml was added for 24 h. RNA-seq was performed on all six samples, as well as samples from two donors that were not infected.
Evidence for multiple roles for grainyhead-like 2 in the establishment and maintenance of human mucociliary airway epithelium.[corrected].
Subject
View SamplesThe airways of the human lung are lined by an epithelium made up of ciliated and secretory luminal cells and undifferentiated p63+ Krt5+ progenitors. The integrity of this epithelium and its ability to act as a selective barrier are critical for normal lung function. In other epithelia there is evidence that transcription factors of the evolutionarily conserved grainyheadlike (GRHL) family play key roles in co-ordinating the expression of numerous proteins required for epithelial morphogenesis, differentiation, remodeling and repair. However, little is known about their function in the adult lung.
Evidence for multiple roles for grainyhead-like 2 in the establishment and maintenance of human mucociliary airway epithelium.[corrected].
Specimen part, Treatment
View SamplesThe airways of the human lung are lined by an epithelium made up of ciliated and secretory luminal cells and undifferentiated p63+ Krt5+ basal cells. The integrity of this epithelium and its ability to act as a selective barrier are critical for normal lung function. In other epithelia there is evidence that transcription factors of the evolutionarily conserved grainyheadlike (GRHL) family play key roles in co-ordinating the expression of numerous proteins required for epithelial morphogenesis, differentiation, remodeling and repair. However, little is known about their function in the adult lung.
Evidence for multiple roles for grainyhead-like 2 in the establishment and maintenance of human mucociliary airway epithelium.[corrected].
Specimen part, Treatment
View SamplesMicroarrays were used to determine transcriptional differences between CCR6+ ILC3s isolated from RorccreTnfsf11fl/fl and Tnfsf11fl/fl small intestine lamina propria.
The Tumor Necrosis Factor Superfamily Member RANKL Suppresses Effector Cytokine Production in Group 3 Innate Lymphoid Cells.
Specimen part
View SamplesRetention of lymphocytes in the intestinal mucosa requires specialized chemokine receptors and adhesion molecules. Here we find that both CD4+CD8+ and CD4+T cells in the intestinal epithelium, as well as CD8+T cells in the intestinal mucosa and mesenteric lymph nodes, express the cell adhesion molecule Crtam upon activation, whereas the ligand of Crtam, Cadm1, is expressed on gut CD103+DCs. Lack of Crtam-Cadm1 interactions in Crtam-/- and Cadm1-/- mice results in loss of CD4+CD8+T cells, which arise from mucosal CD4+T cells that acquire a CD8 lineage expression profile. Following acute oral infection with T. gondii, both WT and Crtam-/- mice mounted a robust TH1 response, but markedly fewer TH17 cells were present in the intestinal mucosa of Crtam-/- mice. The almost exclusive TH1 response in Crtam-/- mice resulted in more efficient control of intestinal T. gondii infection.
CRTAM controls residency of gut CD4+CD8+ T cells in the steady state and maintenance of gut CD4+ Th17 during parasitic infection.
Specimen part, Treatment, Time
View SamplesAmyotrophic Lateral Sclerosis (ALS) results from the selective and progressive degeneration of motor neurons. Although the underlying disease mechanisms remain unknown, glial cells have been implicated in ALS disease progression. Here we examine the effects of glial cell/motor neuron interactions on gene expression, using the hSOD1G93A mouse model of ALS. We detect striking cell autonomous and non-autonomous changes in gene expression in co-cultured motor neurons and glia, revealing that the two cell types profoundly affect each other. In addition, we found a remarkable concordance between the cell culture data, expression profiles of whole spinal cords, and of acutely isolated spinal cord cells, during disease progression in the G93A mouse model, providing validation of the cell culture approach. Bioinformatics analyses identified changes in the expression of specific genes and signaling pathways that may contribute to motor neuron degeneration in ALS, among which are TGF-b signaling pathways. Overall design: RNA-seq profiles of: 1) 43 Sandwich culture samples at 3 different time points (3, 7 and 14 days), in duplicate, in different combinations of genetic background WT/SOD1_G93A mutant glia and WT/SOD1_G93A mutant neurons; 2) 16 spinal cord samples at 4 different time points, WT and SOD1_G93A mutant.
Intricate interplay between astrocytes and motor neurons in ALS.
Sex, Subject, Time
View Samples