This SuperSeries is composed of the SubSeries listed below.
Oxygen regulation of breathing through an olfactory receptor activated by lactate.
Specimen part
View SamplesThe carotid body is a chemoreceptor that senses decreases in blood oxygen to increase breathing in hypoxia.
Oxygen regulation of breathing through an olfactory receptor activated by lactate.
Specimen part
View SamplesThe carotid body is a chemoreceptor that senses decreases in blood oxygen to increase breathing in hypoxia. To look for candidate oxygen sensors in the carotid body, we compared the gene expression of the carotid body to the adrenal medulla, a similar tissue that does not have oxygen sensitivity in adults. Overall design: For each sample, we pooled 18 carotid bodies and 10 adrenal medullas from 10 adult mice.
Oxygen regulation of breathing through an olfactory receptor activated by lactate.
Specimen part, Cell line, Subject
View SamplesMost vertebrate organs are composed of epithelium surrounded by support and stromal tissues formed from mesenchyme cells, which are not generally thought to form organized progenitor pools. Here we use clonal cell labeling with multicolor reporters to characterize individual mesenchymal progenitors in the developing mouse lung. We observe a diversity of mesenchymal progenitor populations with different locations, movements, and lineage boundaries. Airway smooth muscle (ASM) progenitors map exclusively to mesenchyme ahead of budding airways. Progenitors recruited from these tip pools differentiate into ASM around airway stalks; flanking stalk mesenchyme can be induced to form an ASM niche by a lateral bud or by an airway tip plus focal Wnt signal. Thus, mesenchymal progenitors can be organized into localized and carefully controlled domains that rival epithelial progenitor niches in regulatory sophistication.
Mesenchymal cells. Defining a mesenchymal progenitor niche at single-cell resolution.
Specimen part, Treatment
View SamplesNHEK cells were plated at a density of 8 x 10 000/cm2 and the cell cultures were grown for 24 hours before addition of 2 mM N-Acetyl-L-Cystein. RNA obtained from cultures grown for 1, 12 and 24 hrs after NAC treatment were compared to RNA from untreated cells at the corresponding time points. I.e 1 hour NAC treated vs 1 hour untreated cells etc. Each EXTRACT represents an individual mRNA extraction and subsequent cDNA synthesis from a batch of totalRNA originating from one cellculture dish.
Global gene expression analysis in time series following N-acetyl L-cysteine induced epithelial differentiation of human normal and cancer cells in vitro.
Specimen part, Subject, Compound, Time
View SamplesCaco-2 human colon carcinoma cells were seeded at a density of 9 x 10 000 cells/cm2 and the cell cultures were grown for 24 hours before addition of 10 mM N-Acetyl-L-Cystein. RNA obtained from cultures grown for 1, 12 and 24 hrs after NAC treatment were compared to RNA from untreated cells at the corresponding time points. I.e 1 hour NAC treated vs 1 hour untreated cells etc. Each "SAMPLE" represents a biological replicate (i.e. separate cellcultures treated similarily) although I have given identical SAMPLE numbers in pairs.
Global gene expression analysis in time series following N-acetyl L-cysteine induced epithelial differentiation of human normal and cancer cells in vitro.
Specimen part, Cell line, Subject, Compound, Time
View SamplesObjective Recent evidence indicates that the adult hematopoietic system is susceptible to diet-induced lineage skewing. It is not known whether the developing hematopoietic system is subject to metabolic programming via in utero high fat diet (HFD) exposure, an established mechanism of adult disease in several organ systems. We previously reported substantial losses in offspring liver size with prenatal HFD. As the liver is the main hematopoietic organ in the fetus, we asked whether the developmental expansion of the hematopoietic stem and progenitor cell (HSPC) pool is compromised by prenatal HFD and/or maternal obesity. Methods We used quantitative assays, progenitor colony formation, flow cytometry, transplantation, and gene expression assays with a series of dietary manipulations to test the effects of gestational high fat diet and maternal obesity on the day 14.5 fetal liver hematopoietic system. Results Maternal obesity, particularly when paired with gestational HFD, restricts physiological expansion of fetal HSPCs while promoting the opposing cell fate of differentiation. Importantly, these effects are only partially ameliorated by gestational dietary adjustments for obese dams. Competitive transplantation reveals compromised repopulation and myeloid-biased differentiation of HFD-programmed HSPCs to be a niche-dependent defect, apparent in HFD-conditioned male recipients. Fetal HSPC deficiencies coincide with perturbations in genes regulating metabolism, immune and inflammatory processes, and stress response, along with downregulation of genes critical for hematopoietic stem cell self-renewal and activation of pathways regulating cell migration. Conclusions Our data reveal a previously unrecognized susceptibility to nutritional and metabolic developmental programming in the fetal HSPC compartment, which is a partially reversible and microenvironment-dependent defect perturbing stem and progenitor cell expansion and hematopoietic lineage commitment. Overall design: Examination of differentially expressed genes between gestational day 15 (+/- 0.5 days) C57BL/6 mouse fetal livers from diet-induced (60% fat diet) obese or control female mice.
Maternal high-fat diet and obesity compromise fetal hematopoiesis.
No sample metadata fields
View SamplesExtremely premature birth is associated with an increased risk for hypoxic brain injury due to lung immaturity and this results in severe long-term neurodevelopmental impairments. The susceptible cell types in the cerebral cortex at this critical developmental time point and the molecular mechanisms underlying associated gray matter defects in premature infants are not known. Here, we used a human three-dimensional (3D) cellular system to study the effect of changes in oxygen tension on the mid-gestation human cerebral cortex. We identified specific defects in intermediate progenitors, a cortical cell type associated with the expansion of the human cerebral cortex, and show that these are related to the unfolded protein response (UPR) and cell cycle changes. Moreover, we verify these findings in human primary cortical tissue and demonstrate that a modulator of the UPR pathway can prevent the reduction in intermediate progenitors following hypoxia. We anticipate that this human cellular platform will be useful in studying other environmental and genetic factors underlying brain injury in premature infants. We investigated the transcriptional changes associated with exposure to <1% O2 by performing RNA sequencing. Overall design: RNA-seq, 101 bp singlepaired-end reads; minimum of 40 million high quality reads per sample) at 24 and 48 hours (middle and end of <1% O2 for hypoxic condition), as well as after 72 hours of re-oxygenation at 21% O2.
Human 3D cellular model of hypoxic brain injury of prematurity.
Subject, Time
View SamplesMethamphetamine (METH) is an illicit drug which is neurotoxic to the mammalian brain. Numerous studies have revealed significant decreases in dopamine and serotonin levels in the brains of animals exposed to moderate-to-large METH doses given within short intervals of time. In contrast, repeated injections of small nontoxic doses of the drug followed by a challenge with toxic METH doses afford significant protection against monoamine depletion. The present study was undertaken to test the possibility that repeated injections of the drug might be accompanied by transcriptional changes involved in rendering the nigrostriatal dopaminergic system refractory to METH toxicity. Our results confirm that METH preconditioning can provide significant protection against METH-induced striatal dopamine depletion. In addition, the presence and absence of METH preconditioning were associated with substantial differences in the identity of the genes whose expression was affected by a toxic METH challenge.
Methamphetamine preconditioning alters midbrain transcriptional responses to methamphetamine-induced injury in the rat striatum.
Sex, Age, Specimen part, Treatment
View SamplesHCT116 cells were transfected with two different siRNA's targeting either DDX5, an siRNA targeting EBNA1, or no siRNA (mock). The siRNA targeting EBNA1 is used as a negative control since HCT116 cells do not have the EBNA1 gene. RNA was obtained from cultures at 24hrs post-siRNA transfection using the Qiagen RNeasy Minikit (cat. # 74104) with on-column DNase digestion performed as per the manufacturer's protocol. The RNA samples were isolated at 24hrs post-siRNA transfection since this timepoint precedes an impaired G1-to-S phase cell cycle progression phenotype that is evident at 48hrs post-siRNA transfection and so may reveal gene expression changes occuring before this effect on cell cycle. RNA samples were submitted to the Cold Spring Harbor Laboratory Microarray Faciity where cDNA was prepared, labeled, and hybridized to Affymetrix GeneChip Human Gene 1.0 ST microarrays. Data from the arrays were processed using the RMA method with an up-to-data probe set definition (Biostatistics 4:249-264 and Nucleic Acids Research 33(20):e175. Gene set analysis was performed using generally applicable gene set enrichment (BMC Bioinformatics 10:161). The most differentially regulated gene ontology groups were selected with FDR q-value < 0.1.
DDX5 regulates DNA replication and is required for cell proliferation in a subset of breast cancer cells.
Cell line
View Samples