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SRP173671
Mus musculus
12 Downloadable Samples
Illumina HiSeq 2000
Description
During CNS development, the nuclear protein SATB2 is expressed in superficial cortical layers and determines projection neuron identity. In the adult CNS, SATB2 is expressed in pyramidal neurons of all cortical layers and is a regulator of synaptic plasticity and long-term memory. Common variation in SATB2 locus confers risk of schizophrenia whereas rare, de novo structural and single nucleotide variants cause severe intellectual disability and absent or limited speech. To which extent symptoms in SATB2-related human pathologies depend on developmental or adult functions of the protein remains to be established. To characterize differences in SATB2 molecular function in developing vs adult neocortex, we compared SATB2 protein interactomes and SATB2-driven gene expression programs at the two ontogenetic stages by co-IP mass spectrometry and RNAseq analyses, respectively. Our results demonstrated that 1) SATB2 interacts with different protein networks at the two ontogenetic stages, with a switch from transcriptional repression towards organization of chromatin structure and 2) SATB2 determines differential transcriptional programs in neonatal vs adult cortex. Overall design: Analysis of neocortex transcriptomes of adult (3 month old) SATB2-deficient (Satb2flx/flx::Camk2a-Cre ) vs floxed mice
Publication Title
Genes encoding SATB2-interacting proteins in adult cerebral cortex contribute to human cognitive ability.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 21 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Insulin resistance is a sine qua non of Type 2 diabetes (T2D) and a frequent complication of multiple clinical conditions, including obesity, aging, and steroid use, among others. How such a panoply of insults can result in a common phenotype is incompletely understood. Furthermore, very little is known about the transcriptional and epigenetic basis of this disorder, despite evidence that such pathways are likely to play a fundamental role. Here, we compare cell autonomous models of insulin resistance induced by the cytokine tumor necrosis factor-a (TNF) or by the steroid dexamethasone (Dex) to construct detailed transcriptional profiles associated with cellular insulin resistance.
Publication Title
Identification of nuclear hormone receptor pathways causing insulin resistance by transcriptional and epigenomic analysis.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In the present study, we hypothesized that C/EBPa (CCAAT/enhancer-binding protein alpha) plays a role in cell regeneration in response to bronchiolar epithelial cell injury. C/EBPa mediated ciliated cell regeneration after naphthalene bronchiolar epithelial cell injury in vivo. Furthermore, we demonstrated that C/EBPa regulates protease/anti-protease balance after lung injury, and intratracheal treatment with anti-protease (BPTI) restored ciliated cell regeneration after naphthalene injury in CebpaD/D mice.
Publication Title
CCAAT/enhancer binding protein-α regulates the protease/antiprotease balance required for bronchiolar epithelium regeneration.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Deletion of Stat3 induced genes influencing protein metabolism, transport, chemotaxis and apoptosis and decreased the expression of genes mediating lipid synthesis and metabolism. Srebf1 and 2, key regulators of fatty acid and steroid biosynthesis, were decreased in Stat3D/D mice. Stat3 influenced both pro- and anti-apoptotic pathways, regulating and maintaining the balance between a subset of pro- and anti-apoptotic genes that determine cell death or survival. Akt, a known target of Stat3, participates in many Stat3 mediated pathways including Jak-Stat signaling, apoptosis, the MAPK signaling, cholesterol and fatty acid biosynthesis. Deletion of Stat3 from type II epithelial cells altered the expression of genes regulating diverse cellular processes, including cell growth and apoptosis, lipid biosynthesis and metabolism. Stat3 regulates cell formation through a complex regulatory network that likely enhances alveolar epithelial cell survival and surfactant/lipid synthesis, necessary for the protection of the lung during injury.
Publication Title
Gene expression and biological processes influenced by deletion of Stat3 in pulmonary type II epithelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We have previously demonstrated that deletion of the Cebpa gene in the developing fetal mouse lung caused death soon after birth from the failure of lung maturation. Many of the transcriptional pathways regulating morphogenesis of the fetal lung are induced postnatally and mediate repair of the injured lung. We hypothesized that C/EBPa plays a role in protection of the alveolar epithelium following hyperoxia injury of the mature lung. Transgenic Cebpa/ mice in which Cebpa was conditionally deleted from Clara cells (from early gestation) and type II cells (from near-term) were developed. Cebpa/ mice grow normally without any pulmonary abnormalities. Cebpa/ mice were highly susceptible to hyperoxia. Cebpa/ mice died within 4d after hyperoxia associated with severe lung inflammation and altered surfactant components at a time when all control mice survived. Microarrays were analyzed on isolated type II cells at an early stage (24h) of hyperoxia exposure to detect the primary genes influenced by deletion of Cebpa. The associated network analysis revealed the reduced expression of key genes related to surfactant lipid and protein homeostasis, such as Srebf, Scap, Lpcat1, Abca3, Sftpb, and Napsa. Genes for the cell signaling, immune response, and protective antioxidants, including GSH and Vnn-1,3, were decreased in the Cebpa/ mice lung. C/EBPa did not play a critical role in postnatal pulmonary function under normal conditions. In contrast, in the absence of C/EBPa, exposure to hyperoxia caused respiratory failure, supporting the concept that C/EBPa plays an important role in enhancing epithelial cell survival, surfactant lipid homeostasis, and maturation of SP-B from pro-SP-B.
Publication Title
C/EBP{alpha} is required for pulmonary cytoprotection during hyperoxia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 11 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
The goal of this experiment was to compare the genes expressed in malignant peripheral nerve sheath tumors (MPNSTs) that arise in zebrafish as a result of homozygous mutation of the p53 gene or heterozygous mutation of several different ribosomal protein (rp) mutations. Since MPNSTs arise very rarely in wild type zebrafish, it seemed a possibility that p53 and rps may in fact be functioning in similar pathways. The tumors arising from the different mutations had been previously classified as similar by histology, thus the goal of the array experiments was to establish if any molecular signatures could be found that could delineate the p53 from the rp MPNSTs.
Publication Title
Loss of p53 synthesis in zebrafish tumors with ribosomal protein gene mutations.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Pseudomonas aeruginosa use quorum-sensing molecules, including N-(3-oxododecanoyl)-homoserine lactone (C12), for intercellular communication. C12 activated apoptosis in mouse embryo fibroblasts (MEF) from both wild type (WT) and Bax/Bak double knock-out mice (WT MEF and DKO MEF that were responsive to C12, DKOR MEF): nuclei fragmented; mitochondrial membrane potential (??mito) depolarized; Ca2+ was released from the endoplasmic reticulum (ER), increasing cytosolic [Ca2+] (Cacyto); caspase 3/7 was activated. DKOR MEF had been isolated from a nonclonal pool of DKO MEF that were non-responsive to C12 (DKONR MEF). RNAseq analysis, qPCR and western blots showed that WT and DKOR MEF both expressed genes associated with cancer, including paraoxonase 2 (PON2), while DKONR MEF expressed little PON2. Adenovirus-mediated expression of human PON2 in DKONR MEF rendered them responsive to C12: ??mito depolarized, Cacyto increased and caspase 3/7 activated. Human embryonic kidney 293T (HEK293T) cells expressed low levels of endogenous PON2, and these cells were also less responsive to C12. Overexpression of PON2, but not PON2-H114Q (no lactonase activity) in HEK293T cells caused them to become sensitive to C12. Because [C12] may reach high levels in biofilms in lungs of cystic fibrosis (CF) patients, PON2 lactonase activity may control ??mito, Ca2+ release from the ER and apoptosis in CF airway epithelia. Coupled with previous data, these results also indicate that PON2 uses its lactonase activity to prevent Bax- and Bak-dependent apoptosis in response to common proapoptotic drugs like doxorubicin, staurosporine but activates Bax- and Bak-independent apoptosis in response to C12. Overall design: Gene expression profiling of mouse embryo fibroblasts from WT and Bax/Bak double knock-out mice (C12 responsive and non-reponsive cell lines).
Publication Title
Paraoxonase 2 serves a proapopotic function in mouse and human cells in response to the Pseudomonas aeruginosa quorum-sensing molecule N-(3-Oxododecanoyl)-homoserine lactone.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
Primary human bronchial epithelial cells were transduced with control or hYAP(S127A) lentivirus in sphere forming conditions. Bronchospheres were harvested on day 18-20 for RNAseq analysis Overall design: Passage 1 Primary HBECs from 2 independent donors were transduced with control or hYAP lentivirus. 48 hours post infection, cells were plated on transwell inserts in a 50-50 mixture of ALI medium-Cultrex BME reduced growth factor (RGF) to form spheres. Well differentiated bronchospheres were harvested for RNA-seq analysis on day 18-20 by combining 3 wells of each group for each donor.
Publication Title
Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
ShhCre;Mst1/2flx/flx (Mst1/2 D/D) mice were generated to conditionally delete Mst1 and Mst2 from epithelial progenitors during lung morphogenesis. Lungs from E18.5 control and Mst1/2 D/D mice were mechanically and enzymatically dissociated to generate single cell suspension. Epcam(+) cells were isolated using magnetic microbeads.
Publication Title
Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung.
Sample Metadata Fields
Specimen part
View Samples