Project description:We performed single-cell RNA sequencing on epithelial cells, isolated from lungs of normal and tumor-bearing mice, to shed light on the function and phenotype changes of lung epithelial cells in pre-metastatic niche.
Project description:Tissue fibrosis is a common pathological outcome of chronic disease that markedly impairs organ function leading to morbidity and mortality. In the lung, idiopathic pulmonary fibrosis (IPF) is an insidious and fatal interstitial lung disease associated with declining pulmonary function. Single cell RNA sequencing was used to map epithelial cell types of the normal human airway and alveolaor as well as IPF explant tissue.
Project description:Declining lung function in patients with interstitial lung disease is accompanied by epithelial remodeling and progressive scarring of the gas-exchange region. There is a need to better understand the contribution of basal cell hyperplasia and associated mucosecretory dysfunction to the development of idiopathic pulmonary fibrosis (IPF). Single cell RNA sequencing was used to map epithelial cell types of the normal and IPF human airway. Organoid and ALI cultures were used to investigate functional properties of basal cell subtypes. We confirmed that Notch2 maintains undifferentiated basal cells and restrict basal-to-ciliated differentiation, and present evidence that Notch3 functions to restrain secretory differentiation. When characterizing single cell transcriptomes of the IPF lung we found a bias towards accumulation of the secretory primed basal cell subset.
Project description:Epithelial cell homeostasis and renewal in the lung requires the supportive signals from surrounding mesenchymal cells. Single cell RNA-seq analysis was used to examine the gene expression levels of several receptors on the Sftpc+ alveolar type II stem cells. Single cell RNA-seq revealed Ghr, Cxcr2, Cxcr4, and Igf1r expressing cells were all Sftpc+ cells in the normal mouse lung.
Project description:Understanding the molecular and cellular processes involved in lung epithelial regeneration may fuel the development of therapeutic approaches for lung diseases. We combine mouse models allowing diphtheria toxin-mediated damage of specific epithelial cell types and parallel GFP-labeling of functionally dividing cells with single-cell transcriptomics to characterize the regeneration of the distal lung. We uncover cell types, including Krt13+ basal and Krt15+ club cells, detect an intermediate cell state between basal and goblet cells, reveal goblet cells as actively dividing progenitor cells, and provide evidence that adventitial fibroblasts act as supporting cells in epithelial regeneration. We also show that diphtheria toxin-expressing cells can persist in the lung, express specific inflammatory factors, and transcriptionally resemble a previously undescribed population in the lungs of COVID-19 patients. Our study provides a comprehensive single-cell atlas of the distal lung that characterizes early transcriptional and cellular responses to concise epithelial injury, encompassing proliferation, differentiation, and cell-to-cell interactions.
Project description:Mutant KRAS is the most common oncogenic driver of epithelial cancers. Nevertheless, the molecular changes induced by KRAS activation in primary epithelial cells remain unknown. Here, we determined transcriptional changes at single-cell resolution after KRAS activation in distal lung epithelial cell populations. We observed that activating somatic KRAS mutations had the most pronounced effect on alveolar type 2 (AT2) cells, one type of distal lung epithelial progenitor cells, whereas other distal lung epithelial cell types were similar to their wildtype KRAS counterparts. We found that tumor-associated AT2 cells highly expressed EPCAM and SFTPB, but had a significant reduction of STFPC and STFPD expression compared to their normal lung-associated counterparts.