Single-cell RNA-seq reveals novel cell differentiation dynamics during human airway epithelium regeneration
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ABSTRACT:
PROVIDER: PRJNA498675 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10123808.fastq.gz | Fastqsanger.gz | |||
| SRR10123809.fastq.gz | Fastqsanger.gz | |||
| SRR10123810.fastq.gz | Fastqsanger.gz | |||
| SRR10123811.fastq.gz | Fastqsanger.gz | |||
| SRR10123812.fastq.gz | Fastqsanger.gz |
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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.
2019-09-20 | GSE121600 | GEO
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. Four time points (ALI-D0, ALI-D7, ALI-D14, ALI-D21) of regeneration of the airway epithelium for 3 donors.
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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). 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.
2011-06-06 | E-GEOD-22142 | biostudies-arrayexpress
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.
2011-06-07 | GSE22141 | GEO
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2011-06-07 | GSE22142 | GEO
Project description:The extent of lung regeneration following catastrophic damage and the potential role of adult stem cells in such a process remains obscure. Sublethal infection of mice with an H1N1 influenza virus related to that of the 1918 pandemic triggers massive airway damage followed by apparent regeneration. We show here that p63-expressing stem cells in the bronchiolar epithelium undergo rapid proliferation after infection and radiate to interbronchiolar regions of alveolar ablation. Once there, these cells assemble into discrete, Krt5+ pods and initiate expression of markers typical of alveoli. Gene expression profiles of these pods suggest that they are intermediates in the reconstitution of the alveolar-capillary network eradicated by viral infection. The dynamics of this p63-expressing stem cell in lung regeneration mirrors our parallel findings that defined pedigrees of human distal airway stem cells assemble alveoli-like structures in vitro and suggests new therapeutic avenues to acute and chronic airway disease. 3 colonies fron control and H1N1 influenza treated lungs (12 dpi) ,each were picked for whole genome microarray analysis
2011-11-01 | E-GEOD-32600 | biostudies-arrayexpress
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. Four time points (ALI-D0, ALI-D7, ALI-D14, ALI-D21) of regeneration of the airway epithelium for 3 donors.
2011-06-06 | E-GEOD-22144 | biostudies-arrayexpress
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2011-11-01 | E-GEOD-32604 | biostudies-arrayexpress
Project description:The possibility of lung regeneration has been long discounted due to the irreversible nature of chronic lung diseases. However, patients who sustain massive loss of lung tissue during acute infections often recover full pulmonary function. Correspondingly, we previously demonstrated lung regeneration in mice following H1N1 influenza virus infection and implicated p63+Krt5+ distal airway stem cells, or DASCp63/Krt5, in this process. We show here that rare, preexisting DASCp63/K5 undergo a proliferative expansion in response to influenza and lineage-trace to nascent alveoli assembled at sites of interstitial inflammation. We also show that the ablation of DASCp63/Krt5 in vivo prevents the regeneration of lung tissue following influenza leading to pre-fibrotic lesions and deficient oxygen exchange. Finally, we demonstrate that exogenously cloned and propagated DASCp63/Krt5 readily contribute to lung regeneration following transplantation. These data suggest that DASCp63/K5 are required for lung regeneration and may have therapeutic utility in acute and chronic lung diseases. Tracheal epithelium and alveoli of healthy mice were laser capture microdissected for microarray analysis. Damaged lung interstitium (CD45+ region) of influenza infected (75pfu H1N1, 15dpi) mice were also dissected. Duplicates were included for each sample. We used the Affymetrix Mouse Exon 1.0 ST platform
2014-11-20 | E-GEOD-61091 | biostudies-arrayexpress
Project description:Human airway epithelial cells cultured in vitro at air-liquid interface (ALI) form a pseudostratified epithelium that forms tight junctions and cilia, and produces mucin, and are widely used as a model of differentiation, injury, and repair. To assess how closely the transcriptome of ALI epithelium matches that of in vivo airway epithelial cells, we used microarrays to compare the transcriptome of human large airway epithelial cells cultured at ALI with the transcriptome of large airway epithelium obtained via bronchoscopy and brushing. Gene expression profiling showed global gene expression correlated well between ALI cells and brushed cells, but there were some differences. Gene expression patterns mirrored differences in proportions of cell types (ALI have higher percentages of basal cells, brushed cells have higher percentages of ciliated cells), with ALI cells expressing higher levels of basal cell-related genes and brushed cells expressing higher levels of cilia-related genes. Pathway analysis showed ALI cells had increased expression of cell cycle and proliferation genes, while brushed cells had increased expression of cytoskeletal organization and humoral immune response genes. Overall, ALI cells are a good representation of the in vivo airway epithelial transcriptome, but for some biologic questions, the differences in the in vitro vs in vivo environments need to be considered. Affymetrix arrays were used to assess the gene expression of large airway cells cultured in vitro at air-liquid interface (12 samples) and large airway epithelial cells obtained by fiberoptic bronchoscopy of 20 healthy nonsmokers. *** Air-liquid interface Samples not provided in this Series. ***
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