The Toxoplasma type I ROP16 kinase directly activates the host STAT3 and STAT6 transcription factors and regulates the expression of many host genes. However, many of genes lack known STAT3/6 transcription factor binding sites in their promoter regions.
Toxoplasma gondii rhoptry 16 kinase promotes host resistance to oral infection and intestinal inflammation only in the context of the dense granule protein GRA15.
Specimen part
View SamplesThe Toxoplasma type I ROP16 kinase directly activates the host STAT3 and STAT6 transcription factors and when transgenically expressed in the orally virulent type II strain, promotes host resistance to oral challenge.
Toxoplasma gondii rhoptry 16 kinase promotes host resistance to oral infection and intestinal inflammation only in the context of the dense granule protein GRA15.
Specimen part
View SamplesThe motor neurons innervating the muscles of facial expression are organized into somatotopic hindbrain clusters termed subnuclei. Each of the medial, intermediate, dorsolateral, and lateral subnuclei gives rise to a specific branch of the facial motor nerve (cranial nerve VII). How subnucleus-specific gene expression could mediate the accurate development of facial nerve projections was not well understood.
Etv1 Controls the Establishment of Non-overlapping Motor Innervation of Neighboring Facial Muscles during Development.
Sex, Specimen part
View SamplesIn 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.
CCAAT/enhancer binding protein-α regulates the protease/antiprotease balance required for bronchiolar epithelium regeneration.
Specimen part, Treatment
View SamplesDeletion 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.
Gene expression and biological processes influenced by deletion of Stat3 in pulmonary type II epithelial cells.
No sample metadata fields
View SamplesWe 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.
C/EBP{alpha} is required for pulmonary cytoprotection during hyperoxia.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung.
Specimen part
View SamplesPrimary 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.
Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung.
No sample metadata fields
View SamplesShhCre;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.
Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung.
Specimen part
View SamplesMst1 and Mst2 were conditionally deleted from non-ciliated bronchiolar epithelial cells in the mature lung. Bronchiolar epithelial cells from control and Mst1/2 deleted mice were isolated by cell sorting and used for RNA-seq analysis. Overall design: Scgb1a1-rtTA/tetO-Cre/Mst1;2-flx/flx (Mst1/2 D/D) mice were generated to conditionally delete Mst1 and Mst2 from non-ciliated, secretory bronchiolar epithelial cells. Adult mice were maintained on doxycycline food for 16 days to induce deletion of Mst1/2. Lin-/CD326+/CD24-intermediate cells were isolated by fluorescence cell sorting to enrich for the targeted airway epithelial cells. mRNA isolated from Lin-/CD326+/CD24-intermediate cells from control and Mst1/2 D/D mice was pooled and analyzed by RNA-seq to identify transcriptional changes following deletion of Mst1 and Mst2 from mature lung bronchiolar epithelial cells.
Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung.
No sample metadata fields
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