EpCAM⁺CD73⁺ mark epithelial progenitor cells in postnatal human lung and are associated with pathogenesis of pulmonary disease including lung adenocarcinoma

Abstract

Lung injury in mice induces mobilization of discrete subsets of epithelial progenitor cells to promote new airway and alveolar structures. However, whether similar cell types exist in human lung remains unresolved. Using flow cytometry, we identified a distinct cluster of cells expressing epithelial cell adhesion molecule (EpCAM), a cell surface marker expressed on epithelial progenitor cells, enriched in the ecto-5'-nucleotidase CD73 in unaffected postnatal human lung resected from pediatric patients with congenital lung lesions. Within the EpCAM+CD73+ population, a small subset co-express integrin β4 and HTII-280. This population remained stable with age. Spatially, EpCAM+CD73+ cells were positioned along the basal membrane of respiratory epithelium and alveolus next to CD73+ cells lacking EpCAM. Expanded EpCAM+CD73+ cells give rise to pseudostratified epithelium in 2D air-liquid interface or a clonal 3D organoid assay. Organoids generated under alveolar differentiation conditions were cystic-like and lacked robust alveolar mature cell types. Compared with unaffected postnatal lung, congenital lung lesions were marked by clusters of EpCAM+CD73+ cells in airway and cystic distal lung structures lined by simple epithelium of composed of EpCAM+SCGB1A1+ cells and hyperplastic EpCAM+proSPC+ cells. In non-small cell lung cancer (NSCLC), there was a marked increase in EpCAM+CD73+ tumor cells enriched in inhibitory immune checkpoint molecules CD47 and programmed death-ligand 1 (PD-L1), which was associated with poor survival in lung adenocarcinoma. In conclusion, EpCAM+CD73+ cells are a rare novel epithelial progenitor cell in human lung. Importantly, re-emergence of CD73 in lung adenocarcinoma enriched in negative immune checkpoint molecules may serve as a novel therapeutic target.

Extracellular vesicles derived from umbilical cord mesenchymal stromal cells alleviate pulmonary fibrosis by means of transforming growth factor-β signaling inhibition

“…e uMSC-EV particle size was detected using NanoSight. FCM, flow cytometry; IF, immunofluorescence staining; uMSCs, umbilical cord-derived mesenchymal stromal cells; uMSC-EVs, umbilical cord-derived mesenchymal stromal cell-derived extracellular vesicles Ki67 + cells and EpCAM + (maker of epithelial cells) [34] cells were found to be overlapped in the lung tissue sections (Fig. 3).…”

Tumor-infiltrating lymphocytes are functionally inactivated by CD90+ stromal cells and reactivated by combined Ibrutinib and Rapamycin in human pleural mesothelioma

“…All patients gave informed written consent for the usage of surgical material for research purposes, which was approved by the Ethics Commission of the Canton of Bern (KEK-BE: 042/2015). Fresh MPM tissue was dissociated to single cell suspension and quantification and prospective isolation of mesenchymal cell subsets, as well as analysis of TILs was performed as previously described 27 . Following Fc block (eBioscience), single cells were incubated with a panel of fluorescently conjugated human monoclonal antibodies directed at the following epitopes: CD45, CD14, CD31, CD235a, CD73, CD90, EpCAM, PD-L1 (see Table S2 ).…”

Gene Coexpression Network Characterizing Microenvironmental Heterogeneity and Intercellular Communication in Pancreatic Ductal Adenocarcinoma: Implications of Prognostic Significance and Therapeutic Target

“…Finally, the Seurat clusters were determined by ‘FindNeighbors’ and ‘FindClusters’ functions in the Seurat package. The cellular identity of each cluster was identified by the expression of cell type–specific genes: epithelial cells [EPCAM ( 24 ), KRT19 ( 25 )], pancreatic islet [INS ( 26 )], pancreatic acinar cells [CPA1 ( 27 )], immune cells [PTPRC/CD45 ( 28 )], B cells [MS4A1/CD20 ( 29 ), CD79A ( 30 )], T cells [CD3E ( 29 )], myeloid cells [ITGAX/CD11C ( 31 )], endothelial cells [CDH5 ( 32 )], and fibroblasts [COL1A2 ( 33 )].…”