Strategies Utilizing Notch Signaling for Regenerative Potential of the Circulatory System

Notch signaling plays a vital role in various cellular processes and is essential for various developmental and physiological functions. Here, we focus on two processes in the circulatory system – regulating hematopoiesis and maintaining the integrity of the pulmonary vasculature. Hematopoietic stem cells have great potential for treating hematological and immunological diseases through hematopoietic stem cell transplants. However, the limited availability of human leukocyte antigen-matched donors and a sufficient supply of hematopoietic stem cells pose challenges, and the development of an ex vivo culture method capable of preserving hematopoietic stem cells with self-renewal and differentiation capability is highly desired. In this study, we have established a bioengineered ex vivo culture system that mimics the hematopoietic niche found in the liver. We have achieved the maintenance and expansion of functional hematopoietic stem cell and progenitor cells and investigated the role of Notch signaling in promoting expansion with our cultured system. We have also investigated the role of Notch signaling in the context of regulating vascular permeability. While the role of Notch signaling in endothelial cells have been extensively studies, its involvement in maintaining vascular integrity has only recently been explored. In this study, we aimed to investigate the role of Notch transcriptional signaling and identified a novel downstream target gene that regulates vascular permeability in the lung.