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Transcriptome analysis during the time course of regeneration of the human airway mucociliary epithelium

ABSTRACT: The regeneration of the airway mucociliary epithelium involves several sequential events including migration, proliferation, polarization and final differentiation (i.e ciliogenesis). We used microarrays to detail the global programme of gene expression that occurs during regeneration and ciliogenesis of the human airway mucociliary epithelium.

ORGANISM(S): Homo sapiens

PROVIDER: GSE22142 | GEO | 2011/06/07

SECONDARY ACCESSION(S): PRJNA129205

REPOSITORIES: GEO

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Transcriptome analysis during the time course of regeneration of the human airway mucociliary epithelium

Project description:The regeneration of the airway mucociliary epithelium involves several sequential events including migration, proliferation, polarization and final differentiation (i.e ciliogenesis). We used microarrays to detail the global programme of gene expression that occurs during regeneration and ciliogenesis of the human airway mucociliary epithelium. The four time points of regeneration of the airway epithelium (ALI-D0 which corresponds to the end of proliferation step; ALI-D7 which corresponds to the polarization step; ALI-D14 which corresponds to the onset of ciliogenesis and ALI-D21 corresponding to the terminal differentiation step) for RNA extraction and hybridization on Affymetrix microarrays.

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Project description:The regeneration of the airway mucociliary epithelium involves several sequential events including migration, proliferation, polarization and final differentiation (i.e ciliogenesis). The airway mucociliary epithelium is consituted of three main cell types : ciliated cells, secretory cells and basal cells. We used microRNA microrrays to investigate the signature of microRNA during the four step of regeneration of the airway epithelium.

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microRNAs-449 control vertebrate multi-ciliogenesis by repressing Notch signalling

Project description:This SuperSeries is composed of the following subset Series: GSE22141: MicroRNA signature during the time course of regeneration of the human airway mucociliary epithelium GSE22142: Transcriptome analysis during the time course of regeneration of the human airway mucociliary epithelium GSE22143: Transcriptomic impact of microRNAs-449 or microRNAs-34 overexpression in proliferating human airway epithelial cells GSE22144: miRNAs high throughput sequencing profiling of regenerating human airway epithelial cells GSE22145: miRNAs high throughput sequencing profiling of basals cells and columnar cells GSE22146: microRNAs signatures of Xenopus laevis embryo epidermis at stage 11 (non ciliated) and 26 (ciliated) using high throughput sequencing Refer to individual Series

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Project description:The upper airway epithelium is mainly composed of 4 cell types: multiciliated, goblet, secretory and basal cells. It constitutes an efficient first line of defense of the respiratory tract against a large panel of inhaled substances. Upon injury, regeneration of this epithelium through proliferation and differentiation events can restore a proper mucociliary function. In chronic airway diseases, such as chronic obstructive pulmonary disease or asthma, the injured epithelium frequently displays defective repair leading to tissue remodeling, characterized by a loss of multiciliated cells and mucus hyper-secretion. This situation emphasizes the need to accurately delineate the drivers of differentiation dynamics and cell fate in human airway epithelium. We have used single cell transcriptomics to characterize the sequence of cellular and molecular processes taking place during human airway mucociliary epithelium regeneration in vitro. A comparison with single-cell data from fresh human and pig airway samples, and from in vitro mouse tracheal epithelial cells confirmed our findings in several distinct mammalian species. Single-cell RNA-seq in the airways provides novel insights in differentiation dynamics with the identification of alternative cell trajectories, novel cell subpopulations and by mapping the activation and repression of key signaling pathways.

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Mandatory Role of HMGA1 in Human Airway Epithelial Normal Differentiation and Post-injury Regeneration

Project description:Background: High mobility group AT-hook1 (HMGA1) is essential for airway basal cell mucociliary differentiation, barrier integrity and wound repair. HMGA1 expression suppresses the abnormal basal cell differentiation to squamous, inflammatory and epithelial-mesenchymal transition phenotype commonly observed in association with cigarette smoking and chronic obstructive pulmonary disease (COPD). Results: HMGA1 knockdown experiments indicate that when HMGA1 expression is suppressed, the airway basal cells cannot normally differentiate into a mucociliary epithelium, form an intact barrier, and repair following injury. Instead, airway basal cell differentiation was skewed to an abnormal squamous EMT-like phenotype associated with airway remodeling in COPD. This study demonstrates that HMGA1 plays a key role in normal airway differentiation, regeneration of the normal airway epithelium following injury, and suppression of expression of genes related to squamous metaplasia, EMT and inflammation.

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