During this webinar Dr. Anjali Kusumbe will present a new and efficient pipeline for clearing and immunolabeling intact calcified tissues, allowing for superfast, single-cell resolution, and quantitative 3D imaging of skeletal elements and discovery of lymphatic vessels in bones. The application of this rapid imaging technique revealed unexpected lymphatic vascular networks in bones, challenging the conventional belief that bones lack lymphatic vessels. Using high-resolution light-sheet imaging and cell-specific mouse genetics, demonstrated the presence of lymphatic vessels in both mouse and human bones. Furthermore, this research uncovers that lymphatic vessel expand in response to genotoxic stress, driven by VEGF-C/VEGFR-3 signaling and stress-induced IL6. During lymph angiogenesis, the secretion of CXCL12 from proliferating lymphatic endothelial cells emerged as a crucial factor for hematopoietic and bone regeneration. Additionally, lymphatic vessel derived CXCL12 induced the expansion of mature Myh11+ CXCR4+ pericytes, which differentiate into bone cells and contribute to both bone and hematopoietic regeneration. The study suggests that targeting bone lymphatics could serve as a therapeutic strategy to stimulate hematopoietic and bone regeneration, particularly in the context of stress and injury, with implications for age-related impairment of bone regeneration.
