Transcriptomic analysis of Cuvierian Organs regeneration in the sea cucumber Holothuria leucospilota

Sea cucumbers are renowned for their regenerative capabilities, making them ideal models for studying tissue and organ regeneration. Holothuria leucospilota possesses a unique defensive structure, the Cuvierian organ (CO), which is ejected upon threat and regenerates within weeks. However, the molecular mechanisms underlying CO regeneration remain poorly understood. In this study, we induced CO expulsion in H. leucospilota by mechanical stimulation and examined the regeneration process over 31 days. Histological analysis revealed that regeneration initiated with mesothelium formation, followed by connective tissue and epithelium development. Transcriptomic analysis identified numerous differentially expressed genes during regeneration. Key extracellular matrix (ECM)-related genes were upregulated, while matrix protease genes were downregulated. Signaling pathways including Wnt and Hippo were suppressed, whereas apoptosis and cell cycle pathways were activated. Additionally, several structural outer-layer proteins showed altered expression. These results indicate that ECM reorganization and coordinated regulation of cell proliferation and apoptosis are central to CO regeneration. This study provides important insights into the molecular mechanisms of organ regeneration in echinoderms and offers valuable clues for regenerative studies in higher animals.