Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA277526 | ENA |
REPOSITORIES: ENA
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Project description:Cross-species transcriptome profiling identifies new alveolar epithelial type I cell-specific genes
| PRJNA254464 | ENA
Project description:Diseases involving the distal lung alveolar epithelium include chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and lung adenocarcinoma. Accurate labeling of specific cell types is critical for determining the contribution of each to pathogenesis of these diseases. The distal lung alveolar epithelium is comprised of two cell types, alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. While cell type-specific markers, most prominently surfactant protein C (SFTPC), have allowed detailed lineage tracing studies of AT2 cell differentiation and their roles in disease, studies of AT1 cells have been hampered by lack of genes with expression unique to AT1 cells. In this study, we performed genome-wide expression profiling of multiple rat organs alongside purified rat AT2, AT1 and in vitro differentiated AT1-like cells, resulting in identification of 54 candidate AT1 cell markers. Cross-referencing with genes upregulated in human in vitro differentiated AT1-like cells narrowed the potential list to 18 candidate genes. Testing the top four candidate genes at RNA and protein levels revealed GRAM domain 2 (GRAMD2), a protein of unknown function, as highly specific to AT1 cells. RNAseq confirmed that GRAMD2 is transcriptionally silent in human AT2 cells. Immunofluorescence verified that GRAMD2 expression is restricted to the plasma membrane of AT1 cells and is not expressed in bronchial epithelial cells, while RT-PCR confirmed that it is not expressed in endothelial cells. Utilizing GRAMD2 as a new AT1 cell-specific gene will enhance AT1 cell isolation, investigation of alveolar epithelial cell differentiation potential, and contribution of AT1 cells to distal lung diseases.
2016-11-03 | GSE59120 | GEO
Project description:Diseases involving the distal lung alveolar epithelium include chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and lung adenocarcinoma. Accurate labeling of specific cell types is critical for determining the contribution of each to pathogenesis of these diseases. The distal lung alveolar epithelium is comprised of two cell types, alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. While cell type-specific markers, most prominently surfactant protein C (SFTPC), have allowed detailed studies of AT2 cell differentiation and their roles in disease, studies of AT1 cells have been hampered by lack of genes with expression unique to AT1 cells. To address this, we performed genome-wide expression profiling of multiple rat organs alongside purified rat AT2, AT1 and in vitro differentiated AT1-like cells, resulting in identification of 54 candidate AT1 cell markers. Cross-referencing with genes upregulated in human in vitro differentiated AT1-like cells narrowed the potential list to 18 candidate genes. Testing the top four candidate genes at RNA and protein levels revealed GRAM domain 2 (GRAMD2), a protein of unknown function, as unique to AT1 cells, while SCNN1G within lung is restricted to AT1 cells. RNAseq confirmed that GRAMD2 is transcriptionally silent in human AT2 cells. Immunofluorescence of mouse alveoli verified that GRAMD2 expression is restricted to the plasma membrane of AT1 cells. These new AT1 cell-specific genes, with GRAMD2 as a leading candidate, will enhance AT1 cell isolation, investigation of alveolar epithelial cell differentiation potential, and contribution of AT1 cells to distal lung diseases.
2016-11-03 | GSE66627 | GEO
Project description:Alveolar formation increases the surface area for gas-exchange and is key to the physiological function of the lung. Alveolar epithelial cells, myofibroblasts and endothelial cells undergo coordinated morphogenesis to generate epithelial folds (secondary septa) within the saccules to form alveoli. A mechanistic understanding of alveologenesis remains incomplete. We found that the planar cell polarity (PCP) pathway is required in both alveolar epithelial cells and myofibroblasts for alveologenesis. Our studies uncovered a Wnt5a–Ror2–Vangl2 cascade that endows cellular properties and thus novel mechanisms of alveologenesis. This includes PDGF secretion from alveolar type I and type II cells, cell shape changes of type I cells and migration of myofibroblasts. All these cellular properties are conferred by changes in the cytoskeleton and represent a new facet of PCP function. These results extend our current model of PCP signaling from polarizing a field of epithelial cells to conferring new properties at subcellular levels to regulate collective cell behavior.
2020-03-03 | GSE140779 | GEO
Project description:Pandemic influenza H1N1 (pdmH1N1) virus causes mild disease in humans but occasionally leads to severe complications and even death, especially in those who are pregnant or have underlying disease. Cytokine responses induced by pdmH1N1 viruses in vitro are comparable to other seasonal influenza viruses, suggesting the cytokine dysregulation as seen in H5N1 infection is not a feature of the pdmH1N1 virus. However, a comprehensive gene expression profile of pdmH1N1 in relevant primary human cells in vitro has not been reported. Type I alveolar epithelial cells are a key target cell in pdmH1N1 pneumonia. We carried out a comprehensive gene expression profiling using the Affymetrix microarray platform to compare the transcriptomes of primary human alveolar type I-like alveolar epithelial cells infected with pdmH1N1 or seasonal H1N1 virus. Primary type II alveolar epithelial cells were isolated from human non-malignant lung tissue of three patients who underwent lung resection, and cells were differentiated to type I-like before use. Type I-like alveolar epithelial cells were mock infected, or infected with pdmH1N1 or seasonal H1N1 viruses at a multiplicity of infection (MOI) of two. Total RNA was extracted from cells after 8h post-infection, and gene expression profiling was performed using an Affymetrix Human Gene 1.0 ST microarray platform.
2010-10-06 | E-GEOD-24533 | biostudies-arrayexpress
Project description:During the step-wise specification and differentiation of tissue specific multipotent progenitor cells, lineage-specific transcriptional networks are either activated or repressed to orchestrate progenitor cell commitment. The gas exchange niche in the lung contains two major epithelial cell types, alveolar type 1 (AT1) and type 2 (AT2) cells, and the timing of lineage commitment of these cells is critical for correct formation of this niche and postnatal survival. To define the ontogeny of alveolar cell fate in the lung, we used lineage tracing studies combined with spatially specific mRNA transcript and protein expression combined with single cell RNA-seq analysis. These studies reveal that commitment to alveolar epithelial cell fate occurs far earlier than previously appreciated, concomitant with the proximal-distal specification of epithelial progenitors and branching morphogenesis. Using a novel dual lineage tracing system, we show that a small population of alveolar cells express markers of both AT1 and AT2 cells, whose fate is ultimately restricted to a single lineage. However, these bi-transcriptional cells generate only a minor portion of the mature alveolar epithelium. These data reveal a new paradigm of organ formation where early lineage commitment occurs during the nascent stages of development coincident with broad tissue patterning processes including axial patterning of the endoderm and branching morphogenesis.
2019-02-08 | GSE113320 | GEO
Project description:We investigated whether in vitro expansion of human alveolar epithelial type II cells is possible. We found that human endogenous human alveolar epithelial type II cells can be cultured and passaged. The culture system enabled retroviral gene transduction into human alveolar epithelial type II cells. We performed RNA sequencing of human alveolar epithelial type II cells transduced with mutant surfactant protein C or control vector.
2019-06-27 | GSE128291 | GEO
Project description:Cellular senescence due to telomere dysfunction has been hypothesized to play a role in age-associated diseases including idiopathic pulmonary fibrosis (IPF). It has been postulated that paracrine mediators originating from senescent alveolar epithelia signal to surrounding mesenchymal cells and contribute to disease pathogenesis. However, murine models of telomere-induced alveolar epithelial senescence fail to display the canonical senescence-associated secretory phenotype (SASP) that is observed in senescent human cells. In an effort to understand human-specific responses to telomere dysfunction, we modelled telomere dysfunction-induced senescence in a human alveolar epithelial cell line. We hypothesized that this system would enable us to probe for differences in transcriptional and proteomic senescence pathways in vitro and to identify novel secreted protein (secretome) changes that potentially contribute to the pathogenesis of IPF. Following induction of telomere dysfunction, a robust senescence phenotype was observed. RNA-Seq analysis of the senescent cells revealed the SASP and comparisons to previous murine data highlighted species-specific responses to telomere dysfunction. We then conducted a proteomic analysis of the senescent cells using a novel biotin ligase capable of labeling secreted proteins. Candidate biomarkers selected from our transcriptional and secretome data were then evaluated in IPF and control patient plasma. Four novel proteins were found to be differentially expressed between the patient groups: stanniocalcin-1, contactin-1, tenascin C, and total inhibin. Our data show that human telomere-induced, alveolar epithelial senescence results in a transcriptional SASP that is distinct from that seen in analogous murine cells. Our findings suggest that studies in animal models should be carefully validated given the species-specific responses to telomere dysfunction. We also describe a pragmatic approach for the study of the consequences of telomere-induced alveolar epithelial cell senescence in humans.
2021-04-04 | PXD023381 | Pride
Project description:Cross-Species Comparison Identifies Proneural specific patterns of genetic alterations in Glioblastoma
| PRJNA157131 | ENA
Project description:Claudin proteins are major constituents of epithelial and endothelial tight junctions (TJ), where they serve as regulators of paracellular permeability to ions and solutes. Claudin-18, a member of the large claudin family, is highly expressed in lung epithelium. To elucidate the role of claudin-18 in alveolar epithelial barrier function and fluid homeostasis, we generated claudin-18 knockout (C18 KO) mice. Increased alveolar fluid clearance (AFC) observed in C18 KO mice may have accounted for absence of lung edema despite increased alveolar solute permeability compared to wild type (WT) controls. Higher AFC in C18 KO mice was associated with higher Na-K-ATPase activity and increased expression of the Na-K-ATPase β1 subunit compared to WT controls. Consistent with in vivo findings, alveolar epithelial cell (AEC) monolayers derived from C18 KO mice exhibited lower transepithelial electrical resistance (RT) accompanied by increased solute and ion permeability without changes in ion selectivity. Expression of claudin-3 and claudin-4 was markedly increased in whole lung and in freshly isolated AEC from C18 KO mice, while claudin-5 was unchanged. In contrast, occludin, another major component of the TJ complex, was significantly decreased in C18 KO lung. Further analysis revealed rearrangements in the F-actin cytoskeleton in C18 KO MAECM. These findings demonstrate a crucial non-redundant role for claudin-18 in regulation of alveolar epithelial tight junction composition and permeability to ions and solutes. Importantly, increased AFC in C18 KO mice identifies additional roles for claudin-18 in alveolar fluid homeostasis beyond its direct contributions to barrier properties of the alveolar epithelium. Animals with a ubiquitous knockout (C18 KO) were obtained by crossing mice harboring a conditional (floxed) allele of claudin-18 (Cldn18F/F) with CMV-cre deleter mice to delete exons 2 and 3 by Cre/loxP recombination.
2014-04-06 | E-GEOD-48443 | biostudies-arrayexpress