Bronchial epithelium epithelial-mesenchymal plasticity forms aberrant basaloid-like cells in vitro
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PROVIDER: PRJNA797240 | ENA |
REPOSITORIES: ENA
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Project description:Rationale: Although epithelial-mesenchymal transition (EMT) is a common feature of fibrotic lung disease, its role in fibrogenesis is controversial. Recently, aberrant basaloid cells were identified in fibrotic lung tissue as a novel epithelial cell type displaying a partial EMT phenotype. The developmental origin of these cells remains unknown. Objectives: To elucidate the role of EMT in the development of aberrant basaloid cells from human bronchial epithelium by mapping EMT-induced transcriptional changes at the population and single-cell level. Methods: Human bronchial epithelial cells (HBECs) grown as submerged or air-liquid interface (ALI) cultures with or without EMT induction were analyzed by bulk and single-cell RNA-Sequencing. Measurements and Main Results: Comparison of submerged and ALI cultures revealed differential expression of 9,868—protein coding (PC) and long non-coding RNA (lncRNA)—genes and revealed epithelial cell-type-specific lncRNAs. Similarly, EMT induction in ALI cultures resulted in robust transcriptional reprogramming of 6,927—PC and lncRNA—genes. While there was no evidence for fibroblast/myofibroblast conversion, cells displayed a partial EMT gene signature and an aberrant basaloid-like cell phenotype. Conclusions: The substantial transcriptional differences between submerged and ALI cultures highlights that care must be taken when interpreting data from submerged cultures. This work supports that lung epithelial EMT does not generate fibroblasts/myofibroblasts and confirms ALI cultures provide a physiologically relevant system to study aberrant basaloid-like cells and mechanisms of EMT. We provide a catalog of PC and lncRNA genes and a data visualization package for further exploration for potential roles in the lung epithelium in health and lung disease.
2022-04-21 | GSE193683 | GEO
Project description:Rationale: Although epithelial-mesenchymal transition (EMT) is a common feature of fibrotic lung disease, its role in fibrogenesis is controversial. Recently, aberrant basaloid cells were identified in fibrotic lung tissue as a novel epithelial cell type displaying a partial EMT phenotype. The developmental origin of these cells remains unknown. Objectives: To elucidate the role of EMT in the development of aberrant basaloid cells from human bronchial epithelium by mapping EMT-induced transcriptional changes at the population and single-cell level. Methods: Human bronchial epithelial cells (HBECs) grown as submerged or air-liquid interface (ALI) cultures with or without EMT induction were analyzed by bulk and single-cell RNA-Sequencing. Measurements and Main Results: Comparison of submerged and ALI cultures revealed differential expression of 9,868—protein coding (PC) and long non-coding RNA (lncRNA)—genes and revealed epithelial cell-type-specific lncRNAs. Similarly, EMT induction in ALI cultures resulted in robust transcriptional reprogramming of 6,927—PC and lncRNA—genes. While there was no evidence for fibroblast/myofibroblast conversion, cells displayed a partial EMT gene signature and an aberrant basaloid-like cell phenotype. Conclusions: The substantial transcriptional differences between submerged and ALI cultures highlights that care must be taken when interpreting data from submerged cultures. This work supports that lung epithelial EMT does not generate fibroblasts/myofibroblasts and confirms ALI cultures provide a physiologically relevant system to study aberrant basaloid-like cells and mechanisms of EMT. We provide a catalog of PC and lncRNA genes and a data visualization package for further exploration for potential roles in the lung epithelium in health and lung disease.
2022-04-21 | GSE193682 | GEO
Project description:Bronchial epithelium epithelial-mesenchymal plasticity forms aberrant basaloid-like cells in vitro [scRNA-seq]
| PRJNA797244 | ENA
Project description:Bronchial epithelium epithelial-mesenchymal plasticity forms aberrant basaloid-like cells in vitro [bulkRNA-seq]
| PRJNA797245 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-04-21 | GSE193684 | GEO
Project description:Alveolar basal cells differentiate towards secretory epithelial and aberrant basaloid cells in vitro
| PRJNA813874 | ENA
Project description:Long non-coding RNAs (lncRNAs) have emerged recently as key regulatory molecules with diverse roles at almost every level of the regulation of gene expression. The roles of these RNAs in the pathogenesis of cystic fibrosis (CF); a lethal multisystem, autosomal recessive disorder have yet to be explored. Our aim was to examine the expression profile of lncRNA, in the airway epithelium of people with CF. We examined the expression of 30,586 lncRNAs by microarray (Human LncRNA Array v3.0, Arraystar, Inc), in vivo in bronchial cells isolated from endobronchial brushings obtained from CF and non-CF individuals. In total, we identified 1,063 lncRNAs with differential expression between CF and non-CF individuals (fold changeM-bM-^IM-%3, pM-bM-^IM-$0.001). The microarray also contained probes for ~26,109 protein coding transcripts, of which 720 were differentially expressed between CF and non-CF brush samples (fold changeM-bM-^IM-%3, pM-bM-^IM-$0.001). Confirmation of a selection of differentially expressed coding mRNA and lncRNA transcripts such as TLR8 and XIST was achieved using qRT-PCR. Gene ontology bioinformatics analysis, highlighted that many processes over-represented in the CF bronchial epithelium are related to inflammation. These data show a significantly altered lncRNA and mRNA expression profile in CF bronchial cells in vivo. Dysregulation of some of these lncRNAs may play important roles in the chronic infection and inflammation that exists in the lungs of people with CF. RNA was extracted from bronchial epithelial cells obtained from bronchial brushings at bronchoscopy. Three individual biological replicates from each group (Non-CF and CF) were profiled by microarray.
2014-03-10 | E-GEOD-55146 | biostudies-arrayexpress
Project description:19 bronchial epithelial SAGE libraries were constructed and analyzed in this study. Discussed in the study: IDENTIFICATION OF NOVEL LUNG GENES IN BRONCHIAL EPITHELIUM BY SERIAL ANALYSIS OF GENE EXPRESSION Kim M. Lonergan1, Raj Chari1, Ronald J. deLeeuw1, Ashleen Shadeo1, Bryan Chi1, Ming-Sound Tsao2, Steven Jones3, Marco Marra3, Victor Ling1, Raymond Ng1,4, Calum MacAulay5, Stephen Lam5 and Wan L. Lam1 From the 1Department of Cancer Genetics & Developmental Biology, 5Department of Cancer Imaging, 3Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Research Centre, Vancouver, BC, Canada, 2Ontario Cancer Institute / Princess Margaret Hospital, Toronto, ON, Canada, 4the Department of Computer Science, University of British Columbia, Vancouver, BC, Canada A description of the transcriptome of human bronchial epithelium should provide a basis for studying lung diseases including cancer. We demonstrate here that minute epithelial specimens obtained by bronchial brushings afford reliable profiling by serial analysis of gene expression (SAGE) leading to lung gene discovery. We have deduced global gene expression profiles of bronchial epithelium and lung parenchyma, based upon a vast data set of nearly two million sequence tags from 21 SAGE libraries generated from individuals with a history of smoking. Cluster and linear regression analysis demonstrate the repeatability and reproducibility of bronchial SAGE libraries, and suggest that the transcriptome of the bronchial epithelium is distinct from that of lung parenchyma and other tissue types. This distinction is highlighted by the abundant expression of signature genes that reflect tissue-specific and region-specific functions. Through our analysis we have identified novel bronchial-enriched genes and a novel transcript variant for surfactant, pulmonary-associated protein B in lung parenchyma. Conspicuously, gene expression associated with ciliogenesis is evident in bronchial epithelium. Additionally, it is noted that a large number of unmapped tags awaits further investigation. This study represents a comprehensive delineation of the bronchial and parenchyma transcriptomes, identifying more than 20,000 known and hypothetical genes expressed in the human lung, constituting one of the largest human SAGE studies reported to date. Keywords: bronchial epithelium 19 bronchial epithelial SAGE libraries were constructed and analyzed in this study.
2006-07-14 | E-GEOD-3707 | biostudies-arrayexpress
Project description:19 bronchial epithelial SAGE libraries were constructed and analyzed in this study. Discussed in the study: IDENTIFICATION OF NOVEL LUNG GENES IN BRONCHIAL EPITHELIUM BY SERIAL ANALYSIS OF GENE EXPRESSION Kim M. Lonergan1, Raj Chari1, Ronald J. deLeeuw1, Ashleen Shadeo1, Bryan Chi1, Ming-Sound Tsao2, Steven Jones3, Marco Marra3, Victor Ling1, Raymond Ng1,4, Calum MacAulay5, Stephen Lam5 and Wan L. Lam1 From the 1Department of Cancer Genetics & Developmental Biology, 5Department of Cancer Imaging, 3Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Research Centre, Vancouver, BC, Canada, 2Ontario Cancer Institute / Princess Margaret Hospital, Toronto, ON, Canada, 4the Department of Computer Science, University of British Columbia, Vancouver, BC, Canada A description of the transcriptome of human bronchial epithelium should provide a basis for studying lung diseases including cancer. We demonstrate here that minute epithelial specimens obtained by bronchial brushings afford reliable profiling by serial analysis of gene expression (SAGE) leading to lung gene discovery. We have deduced global gene expression profiles of bronchial epithelium and lung parenchyma, based upon a vast data set of nearly two million sequence tags from 21 SAGE libraries generated from individuals with a history of smoking. Cluster and linear regression analysis demonstrate the repeatability and reproducibility of bronchial SAGE libraries, and suggest that the transcriptome of the bronchial epithelium is distinct from that of lung parenchyma and other tissue types. This distinction is highlighted by the abundant expression of signature genes that reflect tissue-specific and region-specific functions. Through our analysis we have identified novel bronchial-enriched genes and a novel transcript variant for surfactant, pulmonary-associated protein B in lung parenchyma. Conspicuously, gene expression associated with ciliogenesis is evident in bronchial epithelium. Additionally, it is noted that a large number of unmapped tags awaits further investigation. This study represents a comprehensive delineation of the bronchial and parenchyma transcriptomes, identifying more than 20,000 known and hypothetical genes expressed in the human lung, constituting one of the largest human SAGE studies reported to date. Keywords: bronchial epithelium
2006-07-14 | GSE3707 | GEO
Project description:Transcriptional profiling of hyperplastic, metaplastic, and dysplastic lesions of the bronchus in comparison with normal bronchial epithelium. The aim was to identify transcripts and cell signalling pathways associated with the development of isolated premalignant lesions and/or lesions combined with each other in the same bronchial epithelium.
2016-05-25 | GSE81819 | GEO