Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection
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PROVIDER: PRJNA147159 | ENA |
REPOSITORIES: ENA
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Project description:This SuperSeries is composed of the following subset Series: GSE32600: Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection (colony) GSE32602: Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection (LCM_Four populations of cells) GSE32604: Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection (stem cell clones NESC,TASC,DASC) Refer to individual Series
2011-11-01 | E-GEOD-32606 | biostudies-arrayexpress
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 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.
2011-11-01 | GSE32600 | 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. H1N1 infected mice were sacrificed at 25 dpi and the lungs were snap frozen and embedded in OCT. Sections were cut and stained for several markers and consecutive sections were used for Laser Capture Microdissection.The PALMM-BM-. Robot Microbeam laser microdissection system (P.A.L.M. GmbH, Bernried, Germany) in combination with a Zeiss microscope was used to dissect out desired cells.Four population of cells were collected namely alveoli, Krt5+,Spc+ and K5&SPC-. Isolated cells were collected in adhesive caps (Carl Zeiss, Inc.) and RNA was extracted using the Pico Pure RNA extraction kit (Arcturus).
2011-11-01 | E-GEOD-32602 | biostudies-arrayexpress
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.
2011-11-01 | GSE32602 | 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.
2011-11-01 | GSE32604 | 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. The long-term self-renewal potential of the putative human stem cell clones (NESC,TASC,DASC) allowed us to isolate independent pedigrees for the analysis of the progeny of a single cell. Expansion of these lines yielded abundant immature cells of known pedigree for a range of differentiation assays to assess lineage potential. All stem cells were grown on feeder layer (3T3).NESC were differentiated using Air liquid interface system (ALI), 3D matrigel system (MAT) and Self assembling sphere culture(SAS). The differentiation potential of TASC and DASC were studied using ALI and MAT systems.
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:To comprehensively study the heterogeneity within distal airway epithelium, we performed single cell transcriptomic analysis of the naive lung samples. Our analysis reveals that distal lung airway epithelial cells are highly heterogenous. We employed supervised clustering to identify a rare group of cells with transcriptional similiarities to embryonic distal lung bud tip progenitors. This approach identified a quiescent progenitor population of airway cells that accounted for all in vitro regenerative activity. Furthermore, these cells were also required for in vivo transplantation, reconstitution of alveoli, and functional recovery of injured mice. These findings indicate that small subpopulations of specialized stem/progenitors are required for effective lung regeneration and could potentially be used as therapeutic adjuncts after major lung injury.
2020-01-23 | GSE129937 | GEO
Project description:To comprehensively study the heterogeneity within distal airway epithelium, we performed single cell transcriptomic analysis of the naive lung samples. Our analysis reveals that distal lung airway epithelial cells are highly heterogenous. We employed supervised clustering to identify a rare group of cells with transcriptional similiarities to embryonic distal lung bud tip progenitors. This approach identified a quiescent progenitor population of airway cells that accounted for all in vitro regenerative activity. Furthermore, these cells were also required for in vivo transplantation, reconstitution of alveoli, and functional recovery of injured mice. These findings indicate that small subpopulations of specialized stem/progenitors are required for effective lung regeneration and could potentially be used as therapeutic adjuncts after major lung injury.
2020-01-23 | GSE130077 | GEO