The early life microbiome plays important roles in host immunological and metabolic development. Because type 1 diabetes (T1D) incidence has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota that predisposes to disease. Using NOD mice that are genetically susceptible to T1D, we examined the effects of exposure to either continuous low-dose antibiotics or pulsed therapeutic antibiotics (PAT) early in life, mimicking childhood exposures. We found that in mice receiving PAT, T1D incidence was significantly higher, microbial community composition and structure differed compared with controls. In pre-diabetic male PAT mice, the intestinal lamina propria had lower Th17 and T reg proportions and intestinal SAA expression than in controls, suggesting key roles in transducing the altered microbiota signals. PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression. These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression, and T-cell populations, accelerating T1D onset in NOD mice.
Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice.
Sex, Specimen part, Disease, Disease stage, Treatment
View SamplesThe pattern of gene transcription in Saccharomyces cerevisiae is strongly affected by the presence of glucose. An increased activity of protein kinase A (PKA), triggered by a rise in the intracellular concentration of cAMP, can account for many of the effects of glucose on transcription. To investigate the requirement of PKA for glucose control of gene expression, we have analyzed global transcription in strains devoid of PKA activity. In S. cerevisiae three genes, TPK1, TPK2, TPK3, encode catalytic subunits of PKA and the triple mutant tpk1 tpk2 tpk3 is unviable. We have worked, therefore, with two strains, tpk1 tpk2 tpk3 yak1 and tpk1 tpk2 tpk3 msn2 msn4, that bear suppressor mutations,. We have identified different classes of genes that can be induced, or repressed, by glucose in the absence of PKA. Among these genes, some are also controlled by a redundant signalling pathway involving PKA activation, while others do not respond to an increase in cAMP concentration. On the other hand, among genes which do not respond to glucose in the absence of PKA, some show a full response to increased cAMP levels, even in the absence of glucose, while others appear to require the cooperation of different signalling pathways.
Transcriptional responses to glucose in Saccharomyces cerevisiae strains lacking a functional protein kinase A.
Treatment, Time
View SamplesSingle-cell expression profiling by RNA-Seq promises to exploit cell-to-cell variation in gene expression to reveal regulatory circuitry governing cell differentiation and other biological processes. Here, we describe Monocle, a novel unsupervised algorithm for ordering cells by progress through differentiation that dramatically increases temporal resolution of expression measurements. This reordering unmasks switch-like changes in expression of key regulatory factors, reveals sequentially organized waves of gene regulation, and exposes regulators of cell differentiation. A functional screen confirms that a number of these regulators dramatically alter the efficiency of myoblast differentiation, demonstrating that single-cell expression analysis with Monocle can uncover new regulators even in well-studied systems. Overall design: We selected primary human myoblasts as a model system of cell differentiation to investigate whether ordering cells by progress revealed new regulators of the process. We sequenced RNA-Seq libraries from each of several hundred cells taken over a time-course of serum-induced differentiation. Please note that this dataset is a single-cell RNA-Seq data set, and each cell comes from a capture plate. Thus, each well of the plate was scored and flagged with several QC criteria prior to library construction, which are provided as sample characteristics; CONTROL indicates that this library is a off-chip tube control library constructed from RNA of approximately 250 cells and ''DEBRIS'' indicates that the well contained visible debris (and may or may not include a cell). Libraries marked DEBRIS thus cannot be confirmed to come from a single cell.
The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells.
No sample metadata fields
View SamplesCombined transcriptomic and functional analyses of HCC cells at single-cell level were performed to assess CSC heterogeneity. Overall design: Single-cell transcriptome analyses of two HCC cell lines (HuH-1 and HuH-7) and one patient-derived circulating tumor cells by using SMART-Seq protocol ***Due to patient privacy concerns, the submitter declares that patient data will be submitted to dbGaP.***
Single-cell analysis reveals cancer stem cell heterogeneity in hepatocellular carcinoma.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression in whole lung and pulmonary macrophages reflects the dynamic pathology associated with airway surface dehydration.
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View SamplesScnn1b-Tg mice overexpress the beta subunit of the epithelial sodium channel (Scnn1b) in airway Club cells. The general phenotype of these mice is described in three published manuscripts (Mall et al. 2004, Nature Medicine, 10(5):487-93; Mall et al. 2008, Am J Respir Crit Care Med. 177(7):730-42; and Livraghi-Butrico et al. 2012, Physiol. Genomics 44(8):470-84. Briefly, overexpression of the Scnn1b transgene in airway Club cells leads to hyperabsorption of sodium from the airway surface liquid, dehydrated airway surface liquid and mucus, and reduced mucus clearance associated with accumulation of mucus plugs/plaques. The data provided here represents mRNA expression data from disseccted whole trachea (distal and proximal ends cut 3-4 cartliage rings below the larynx and just above the bifurcation, respectively) from male WT and Scnn1b-Tg littermates (C57Bl/6NTac background) at 4 time points [postnatal days (PND) 0, 3, 10, and 42]. PND 0 trachea are histologically normal, a tracheal mucus plug/obstruction develops around PND 3, the plug is receding to more distal airways by PND 10, and the trachea is again histologically normal by PND 42. The data from the WT mice provides a global look at mRNA changes across time, while the data from the Scnn1b-Tg line provides mRNA data that allows differential gene expression due to mucus obstruction to be queried.
Gene expression in whole lung and pulmonary macrophages reflects the dynamic pathology associated with airway surface dehydration.
No sample metadata fields
View SamplesScnn1b-Tg mice overexpress the beta subunit of the epithelial sodium channel (Scnn1b) in airway Club cells. The general phenotype of these mice is described in three published manuscripts (Mall et al. 2004, Nature Medicine, 10(5):487-93; Mall et al. 2008, Am J Respir Crit Care Med. 177(7):730-42; Livraghi-Butrico et al. 2012, Physiol. Genomics 44(8):470-84; and Livraghi-Butrico et al. 2012, Mucosal Immunology 5(4):397-408). Briefly, overexpression of the Scnn1b transgene in airway Club cells leads to hyperabsorption of sodium from the airway surface liquid, which causes airway surface liquid and mucus dehydration, resulting in reduced mucus clearance and airway mucus obstruction. The data provided here represents mRNA expression data from dissected whole trachea (distal and proximal ends were cut 3-4 cartilage rings below the larynx and just above the bifurcation, respectively) from male WT and Scnn1b-Tg littermates (C57Bl/6N Tac background) at 4 time points [postnatal days (PND) 0, 3, 10, and 42]. Histologically, PND 0 trachea are normal, a tracheal mucus plug/obstruction develops around PND 3 and typically recedes to the intrapulmonary airways after PND 10, and the trachea is again histologically normal by PND 42. The data from the WT mice provides a global look at mRNA post-natal developmental changes, while the data from the Scnn1b-Tg line provides mRNA data that allows differential gene expression due to airway mucus obstruction to be queried.
Gene expression in whole lung and pulmonary macrophages reflects the dynamic pathology associated with airway surface dehydration.
No sample metadata fields
View SamplesScnn1b-Tg mice overexpress the beta subunit of the epithelial sodium channel (Scnn1b) in airway Club cells. The general phenotype of these mice is described in three published manuscripts (Mall et al. 2004, Nature Medicine, 10(5):487-93; Mall et al. 2008, Am J Respir Crit Care Med. 177(7):730-42; Livraghi-Butrico et al. 2012, Physiol. Genomics 44(8):470-84; and Livraghi-Butrico et al. 2012, Mucosal Immunology 5(4):397-408). Briefly, overexpression of the Scnn1b transgene in airway Club cells leads to hyperabsorption of sodium from the airway surface liquid, which causes airway surface liquid and mucus dehydration, resulting in reduced mucus clearance and airway mucus obstruction. The data provided here represents mRNA expression data from disseccted whole lung from male WT and Scnn1b-transgenic littermates (C57Bl/6NTac background) at 4 time points [postnatal days (PND) 0, 3, 10, and 42]. Histologically, PND 0 lungs are normal, at PND 3 the intrapulmonary airways exhibit transient and spotty Club cell necrosis, and by PND 10 airway mucus obstruction is evident in the proximal portion of the intrapulmonary main stem bronchus. At PND 42, Scnn1b-Tg lungs are charactyerized by chronic low level inflammation, with activated macrophages, neutrophilia, eosinophilia and increased incidence of bronchus-associated lymphoid tissue. The data from the WT mice provides a global look at mRNA post-natal developmental changes, while the data from the Scnn1b-transgenic line allows differential gene expression due to airway surface liquid dehydration and mucus obstruction to be queried.
Gene expression in whole lung and pulmonary macrophages reflects the dynamic pathology associated with airway surface dehydration.
No sample metadata fields
View SamplesCentral corneal thickness (CCT) exhibits broad variability. We determined the corneal gene expression profile three mouse strains with distinct corneal thickness: C57BLKS/J (88.6 um), SJL/J (123.5 um), and C57BL/6J (100.1 um).
Genetic dependence of central corneal thickness among inbred strains of mice.
No sample metadata fields
View Samplesbulk breast tumor RNA from patient
X chromosomal abnormalities in basal-like human breast cancer.
No sample metadata fields
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