Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-Cell RNA-Seq Analysis of long-term transplanted single-cell-derived mouse DASC in host lung

ABSTRACT: Distal airway stem cell (DASC) expressing basal cell restrictive transcription factor p63 and keratin-5 (Krt5) has a strong ability of regeneration after lung injury. Such cells are originated from primitive progenitors in distal airways and could expand/migrate to inflamed damaged lung parenchymal region to form ‘KRT5 pods’ once activated by various types of tissue injury. We isolated the mouse DASC and transplanted the GFP-labelled mDASC into the bleomycin-injured mouse lung by intratracheal instillation. Mice were sacrificed at 30 and 90 days post transplantation and their lung tissue were harvest to detect GFP signal by fluorescence stereomicroscope, the region of which was dissect for single cell-RNA-seq (scRNA-seq). We utilized scRNA-seq to trace the fate of transplanted mDASCs at 30 days and 90 days post transplantation, which revealed cell types differentiated from the transplanted DASCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE168573 | GEO | 2021/03/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

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

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. DASC stem cells were ablated by Dtox treatment in Krt6:DTR mouse model. Control and stem cell ablated lungs were analyzed. We used the Affymetrix Mouse Exon 1.0 ST platform

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

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

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

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

2014-11-20 | GSE60830 | GEO

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

2014-11-20 | GSE60829 | GEO

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

2014-11-20 | GSE60828 | GEO

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 (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.

2014-11-20 | GSE61091 | GEO

Lung extracellular matrix modulates KRT5+ basal cell activity in pulmonary fibrosis

Project description:Aberrant expansion of KRT5+ basal cells in the distal lung accompanies progressive alveolar epithelial cell loss and tissue remodelling during fibrogenesis in idiopathic pulmonary fibrosis (IPF). The mechanisms determining activity of KRT5+ cells in IPF have not been delineated. Here, we show an association between KRT5+ cells in human fibrotic lung and regional differences in collagen topography. In vitro, KRT5+ cell migratory characteristics and expression of remodelling genes are modulated by extracellular matrix (ECM) composition and organisation. Mass spectrometry-based proteomics revealed compositional differences in the matrisome secreted by primary human lung fibroblasts (HLF) from IPF patients compared to controls. Over-expression of ECM glycoprotein, Secreted Protein Acidic and Cysteine Rich (SPARC) in the IPF HLF matrisome restricts KRT5+ cell migration in vitro. Together, our findings demonstrate that changes to the ECM in IPF directly influence KRT5+ cell behaviour and function contributing to remodelling events in the fibrotic niche.

2023-09-28 | PXD037236 | Pride