Project description:This dataset contains single-cell RNA sequencing (scRNA-seq) data from human lung transplant recipients.Lung tissue samples were collected from both CLAD patients and donor to assess cellular heterogeneity and gene expression dynamics.
Project description: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.
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