Mesothelial cell plasticity and function

Su, Yiqun (2025): Mesothelial cell plasticity and function: insights from in vivo lineage tracing, injure models, and human-derived cell studies. Dissertation, LMU München: Medizinische Fakultät

Abstract

Mesothelial cells compose a single layer of cobblestone-shaped epithelial cells that cover the surfaces of the peritoneal, pleural, and pericardial body cavities. as well as most internal organs. The mesothelium functions as a critical protective barrier, defending against pathogens and tumor cells through inflammatory and immune responses when injured or exposed to foreign agents. It maintains a smooth, non-adhesive surface to support organ mobility and rapidly repairs itself following damage, typically restoring integrity within days. Disruption of this repair process can lead to pathological changes in the serosal membrane, resulting in adhesions, fibrosis, endometriosis, cancer progression, or metastatic spread. In this study, we developed inducible CreER knock-in reporter mouse lines, providing a precise tool to trace mesothelial cells in vivo. This system enabled us to analyze the clonal expansion of mesothelial cells at different life stages, from neonatal to adult mice, thereby gaining insights into their distinct proliferative capacities during physiological development and throughout life, at single cell resolution. To further explore mesothelial cell function under pathological conditions, we created a series of disease models, including injury-induced damage, pulmonary fibrosis, and postoperative adhesion models. These models allowed us to systematically study how mesothelial cells respond to and participate in various disease processes, revealing their role in injury response and potential contributions to fibrosis and adhesion formation, at single cell resolutions. In addition to in vivo models, we have developed an ex vivo tissue culture system as well as a primary human mesothelial cell culture system. These platforms enabled detailed examination of the dynamics of human mesothelial cells in response to various stimuli, linking experimental results to human biological processes. Collectively, these models provide a comprehensive approach to studying mesothelial cell behavior under physiological and pathological conditions, laying the foundation for future studies of therapeutic interventions for mesothelial-related diseases. Overall, our study established advanced in vivo and ex vivo models to comprehensively investigate mesothelial cell behavior, revealing their roles in development, homeostasis, and disease, and setting the stage for future therapeutic research targeting mesothelial-related pathologies.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Mesothelial Cells, Lineage Tracing, Disease Models
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 24. Oktober 2025
• 1. Bericht­erstatter:in: Behr, Jürgen