Retinal detachment is a major cause of blindness due to penetrating trauma and ocular inflammation, and is often observed in many patients following cataract extraction surgery. When the retinal photoreceptors detach from their epithelium, stress signals and apoptotic pathways are initiated that will lead to loss of vision, however accelerating the reattachment of these cells can prevent photoreceptor death and subsequent vision loss. To determine the genes involved in this process, we performed a microarray screen using a mouse model or retinal detachment in conjunction with a P2Y2 agonist previously demonstrated to hasten retinal reattachment.
Expression profiling after retinal detachment and reattachment: a possible role for aquaporin-0.
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View SamplesThe lung is the entry site for Bacillus anthracis in inhalation anthrax, the most deadly form of the disease. Spores must escape through the alveolar epithelial cell (AEC) barrier and migrate to regional lymph nodes, germinate and enter the circulatory system to cause disease. Several mechanisms to explain alveolar escape have been postulated, and all these tacitly involve the AEC barrier. In this study, we incorporate our primary human type I AEC model, microarray gene profiling and gene enrichment analysis to study the response of AEC to B. anthracis, (Sterne) spores at 4 and 24 hours post-exposure. Spore exposure altered gene expression in AEC after 4 and 24 hours and differentially expressed genes (1.3 fold, p 0.05) included CCL4/MIP-1 (4 hours), CXCL8/IL-8 (4 and 24 hours) and CXCL5/ENA-78 (24 hours). Gene enrichment analysis revealed that pathways involving cytokine or chemokine activity, receptor binding, and innate immune responses to infection were prominent. Microarray results were confirmed by qRT-PCR and multiplex ELISA assays. Chemotaxis assays demonstrated that spores induced the release of biologically active neutrophil and monocyte chemokines, and that CXCL8/IL-8 was the major neutrophil chemokine. The small or sub-chemotactic doses of CXCL5/ENA-78, CXCL3/GRO and CCL20/MIP-3 may contribute to chemotaxis by priming effects. These data provide the first whole transcriptomic description of the human type I AEC initial response to B. anthracis spore exposure, and contribute to an increased understanding of the role of AEC in the pathogenesis of inhalational anthrax.
No associated publication
Sex, Specimen part, Race, Subject
View SamplesThe respiratory system is a complex network of many cell types, including subsets of macrophages and dendritic cels, that work together to maintain steady-state respiration. Due to limitations in acquiring cells from healthy human lung, these subsets remain poorly characterized transcriptionally and phenotypically. We set out to systemically identify these subsets in human airways, by developing a schema of isolating large numbers of cells by whole lung bronchoalveolar lavage. Six subsets of phagocytic antigen presenting cells were consistently observed, which varied in their ability to internalize bacterial particles. Subsets could be further separated by their inherent capacities to upregulate CD83, CD86, and CCR7. Whole genome transcriptional profiling revealed a clade of true dendritic cells distinct from a macrophage/monocyte clade. Each clade, and each member of both clades, could be discerned by specific genes of increased expression, which would serve as markers for future studies in healthy and diseased states.
Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets.
Sex, Age
View SamplesThe overall goal of this project is to investigate the role of TGF-beta signaling in epithelial cells as it pertains to the orientation of muscle fibers in the soft palate during embryogenesis. Here, we first conducted gene expression profiling of the anterior and posterior portions of the palate from wild-type mice. In addition, we also conducted gene expression profiling of the posterior palate in mutant mice with an epithelium-specific conditional inactivation of the Tgfbr2 gene. The latter mice provide a model of submucosal cleft palate, which is a congenital birth defect commonly observed in many syndromic conditions.
TGFβ regulates epithelial-mesenchymal interactions through WNT signaling activity to control muscle development in the soft palate.
Sex, Specimen part
View SamplesThe overall goal of this project is to investigate the role of Erk2-mediated signaling in regulating the cellular metabolism of cranial neural crest (CNC) cells during palate development. Here, we conducted gene expression profiling of palate tissue from wild type mice as well as those with a neural crest specific conditional inactivation of the Erk2 gene. The latter mice exhibit micrognathia, tongue defects and cleft palate, which is among the most common congenital birth defects and observed in many syndromic conditions.
Disruption of the ERK/MAPK pathway in neural crest cells as a potential cause of Pierre Robin sequence.
Sex, Specimen part
View SamplesYAMC murine colonic epithelial cells were repeatitively treated with commensal bacteria-polarized macrophages or 4-HNE. Following 10 treatments, 25 clones were selected to engraft immunodeficient mice, and 10 out of 25 clones grew tumors in these mice. To explore gene expression associated with cellular transformation, whole-genome profiling was performed on 10 transformed clones and compared with untreated YAMC controls using Illumina Mouse WG-6 v2.0 Expression BeadChip.
Commensal bacteria drive endogenous transformation and tumour stem cell marker expression through a bystander effect.
Age, Specimen part, Cell line, Treatment
View SamplesThe overall goal of this project is to investigate the contribution of the inferior alveolar nerve (IAN) towards cellular mechanisms required for regeneration of the murine incisor. Here, we conducted gene expression profiling of adult murine incisor dental mesenchyme tissue following two weeks after unilateral resection of the IAN from both the denerved and contralateral incisor of five wild-type mice.
Secretion of shh by a neurovascular bundle niche supports mesenchymal stem cell homeostasis in the adult mouse incisor.
Sex, Specimen part
View SamplesThe overall goal of this project is to investigate the role of TGF-beta signaling in tissue-tissue interactions between myogenic precursors of craniofacial muscles and cranial neural crest cells (CNCCs). Here, we conducted gene expression profiling of the tongue bud from mice at embryonic day E13.5 with a CNCC-specific conditional inactivation of the TGF-beta receptor type 1 gene Alk5. These mice provide a model of microglossia as well as disrupted extraocular and masticatory muscle development, which are congenital birth defects commonly observed in several syndromic conditions.
ALK5-mediated transforming growth factor β signaling in neural crest cells controls craniofacial muscle development via tissue-tissue interactions.
Sex, Specimen part
View SamplesThe overall goal of this project is to investigate the role of TGF-beta signaling in tissue-tissue interactions between myogenic precursors of craniofacial muscles and cranial neural crest cells (CNCCs). Here, we conducted gene expression profiling of the mandibular arch from mice at embryonic day E11.5 with a CNCC-specific conditional inactivation of the TGF-beta receptor type 1 gene Alk5. These mice provide a model of microglossia as well as disrupted extraocular and masticatory muscle development, which are congenital birth defects commonly observed in several syndromic conditions.
ALK5-mediated transforming growth factor β signaling in neural crest cells controls craniofacial muscle development via tissue-tissue interactions.
Sex, Specimen part
View SamplesThe overall goal of this project is to investigate the role of TGF-beta signaling in regulating the cellular metabolism of cranial neural crest (CNC) cells during palate development. Here, we conducted gene expression profiling of primary mouse embryonic palatal mesenchymal (MEPM) cells from wild type mice as well as those with a neural crest specific conditional inactivation of the Tgfbr2 gene. The latter mice provide a model of cleft palate, which is among the most common congenital birth defects and observed in many syndromic conditions.
Modulation of lipid metabolic defects rescues cleft palate in Tgfbr2 mutant mice.
Specimen part
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