As a complex multifunctional organ, lung comprises trachea, bronchi, bronchioles and alveoli from proximal to distal in anatomy, which is essential for its gas exchange and host defense functions. There are various types of epithelial cells at different locations of these structures, maintaining and repairing the epithelial layer of each region. Recently scientists have reported a stem-cell population termed BASCs (bronchioalveolar stem cells) that are located at the bronchioalveolar-duct junctions (BADJs) and coexpress club cell as well as AT2-cell markers.
Dr. Guangdun Peng, a principal investigator from Guangzhou Institute of Biomedicine and Heath, Chinese Academy of Sciences and Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), collaborated with Dr. Bin Zhou and Dr. Hongbin Ji from Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, found BASCs hold the potential to differentiate into multiple cell lineage and confirmed the genetic evidence for the in vivo function of BASCs for lung repair and regeneration. This finding entitled “Lung regeneration by multipotent stem cells residing at the bronchioalveolar duct junction” were published online in the journal Nature Genetics on February 18, 2019.
In the study, BASCs give rise to club cells and ciliated cells after bronchiolar injury, while contributing to AT1 and AT2 cells after alveolar injury, demonstrating the pluripotency and differentiation ability of BASCs. They characterized the BASCs cells by dual-recombinase based lineage-tracing system and identified the molecular properties of BASCs at single-cell level. scRNA-seq analysis results showed that BASCs are a transcriptomically distinct population located between the populations of AT2 and club cells. The heterogeneity of BASCs also reflects the characteristics of stem cells that differentiate into different potentials. Their work also confirmed the multipotency of BACs to differentiate into either bronchiolar or alveolar epithelial-cell lineages after different lung injuries. The exploration of lung multipotent stem cells and the confirmation of its differentiating potential provides novel insights into approaches for treating pulmonary diseases and research on lung injury and regeneration.
Dr. Peng’s lab, a member of the Center of Cell Lineage and Atlas (CCLA) of Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), is aiming to implement cutting-edge technologies to investigate the fundamental mechanisms of stem cell lineage segregation and to promote the translational application of functional stem cells. The spatial transcriptome and high-throughput automated single-cell sequencing technology developed in Peng’s lab is able to resolve in situ stem cell dynamic transition and facilitate studies on developmental biology and stem cell lineage.