Associate Professor Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangdong, China (People's Republic)
Abstract: During respiration, the lungs experience mechanical stress, and these physiological forces impact cellular destiny and tissue equilibrium. Pulmonary neuroendocrine cells (PNECs) serve as sensory epithelial cells, communicating the status of the airways to the brain through sensory neurons and locally through the release of calcitonin gene-related peptide (CGRP) and γ-aminobutyric acid (GABA). Upon lung injury, these neuroendocrine cells multiply and differentiate into various cell types to facilitate the repair of the epithelium. A minority of these neuroendocrine cells act as stem cells, exhibiting characteristics of traditional stem cells. The majority of them engage in self-renewal through proliferation following injury, while others migrate to the site of damage. Approximately one week post-injury, specific cells, often singular within each cluster, shed their neuroendocrine identity (dedifferentiate), undergo a period of transit amplification, and then redifferentiate into alternative cell fates, resulting in the formation of extensive clonal patches for tissue repair. Nonetheless, how PNECs integrate mechanical signals from respiratory forces in vivo remain elusive. After unilateral lung airway ligation, we lineage-labeled PENCs using CGRPCreERT2; R26LSL-tdtomato mice and examined reprogram following the Naphthalene injury and we found clonal repair patches reduce after Naphthalene induced injury within two weeks.Furthermore our scRNA-seq data showed that mechanical force sensing ion channels-Piezo2 was upregulated in PNECs after blockage of mechanical force and inhibition of Piezo2 promoted the growth of clonal repair patches.We conclude that respiratory forces play crucial role for PENC stem cell differentiation into the repair lineage. The mechanism how PNECs integrate mechanical signals in their microenvironment remains a mystery and requires further research.
Funding Source: This work was supported in part by National Key R&D Program of China (2024YFC3405600,SQ2024YFA1100190)，National Natural Science Foundation of China(32270854,32161160322,92469301)
