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P63+/Krt5+ Distal Airway Stem Cells are Essential for Lung Regeneration (tracheal epithelium and alveoli)

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE61091 | GEO | 2014/11/20

SECONDARY ACCESSION(S): PRJNA260211

REPOSITORIES: GEO

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p63+/Krt5+ Distal Airway Stem Cells are Essential for Lung Regeneration (tracheal epithelium and alveoli)

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

p63+/Krt5+ Distal Airway Stem Cells are Essential for Lung Regeneration (Dtox treatment)

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. The transplanted DASC ameliorated influenza-induced lung injury. These data suggest that DASCp63/K5 are required for lung regeneration and may have therapeutic utility in acute and chronic lung diseases.

2014-11-20 | GSE60829 | GEO

p63+/Krt5+ Distal Airway Stem Cells are Essential for Lung Regeneration (transplanted and damaged)

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. The transplanted DASC ameliorated influenza-induced lung injury. These data suggest that DASCp63/K5 are required for lung regeneration and may have therapeutic utility in acute and chronic lung diseases.

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p63+/Krt5+ Distal Airway Stem Cells are Essential for Lung Regeneration (before and after in vitro differentiation)

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2014-11-20 | GSE60828 | GEO

p63+/Krt5+ Distal Airway Stem Cells are Essential for Lung Regeneration (Dtox treatment)

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2014-11-20 | E-GEOD-60829 | biostudies-arrayexpress

p63+/Krt5+ Distal Airway Stem Cells are Essential for Lung Regeneration (transplanted and damaged)

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. The transplanted DASC ameliorated influenza-induced lung injury. These data suggest that DASCp63/K5 are required for lung regeneration and may have therapeutic utility in acute and chronic lung diseases. Transplanted DASC cells incorporated into damaged host lung were laser capture microdissected and analyzed. Duplicate mice were included. We used the Affymetrix Mouse Exon 1.0 ST platform

2014-11-20 | E-GEOD-60830 | biostudies-arrayexpress

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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. The transplanted DASC ameliorated influenza-induced lung injury. These data suggest that DASCp63/K5 are required for lung regeneration and may have therapeutic utility in acute and chronic lung diseases. Stem cells before and after in vitro differentiation were subjected to whole genome microarray analysis. Duplicates were included for each sample. We used the Affymetrix Mouse Exon 1.0 ST platform

2014-11-20 | E-GEOD-60828 | biostudies-arrayexpress

Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection (LCM_Four populations of cells)

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2011-11-01 | E-GEOD-32600 | biostudies-arrayexpress

Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection (colony)

2011-11-01 | GSE32600 | GEO