Human primary airway basal cells display a continuum of molecular phases from health to disease in COPD

Airway basal cells are crucial for regeneration of the human lung airway epithelium, and are thought to be important contributors to chronic obstructive pulmonary disease (COPD). However, to reveal how basal cells contribute to disease, the basal cells need to be further characterized. We aimed to study primary human basal cells from healthy donors and COPD patients in order to identify key differences that could further our understanding of the disease mechanisms. In this study, we optimized a sorting protocol for primary human basal cells dependent on cell size and NGFR expression. The basal cell population was found to be heterogeneous in contrast to cultured basal cells. In addition, significant differences such as KRT14 expression was found exclusively in cultured cells. Also, colony-forming capacity was significantly increased in cultured cells showing a clonal enrichment in vitro. Next, by single cell RNA sequencing on primary basal cells from healthy donors and COPD patients, the gene expression changes revealed a continuum ranging from healthy basal cell signatures to diseased basal cells phenotypes. We identified several upregulated genes that may be indicative of COPD, such as stress response related genes GADD45B and AHSA1, along with genes involved in the response to hypoxia such as CITED2 and SOD1. Taken together, the presence of both healthy and diseased basal cells in stage IV COPD demonstrates the potential for regeneration through the discovery of novel therapeutic targets. In addition, we show the importance of studying primary basal cells when investigating disease mechanisms in the human lung. Comparing primary human basal cells from healthy and COPD donors ----------------------------------------------------- Authors state "material from EU patients are protected by GDPR and can therefore not be shared". Thus, this dataset is incomplete. Nextseq1.Sample2 in Raw_Reads.csv is COPD 1 to 3. No additonal information to differentiate among the 3 is provided.