Scientists have recently identified key factors which interact to regulate stem cell development and tissue regeneration. Therapies to regenerate diseased or injured organs will benefit from an in-depth knowledge of how stem cells and progenitor cells develop into complex tissues and organs. Previous research has implicated several factors in the regulation of blood (hematopoietic) stem cell formation and self-renewal. These include prostaglandin E2 (PGE2) and a series of factors known as the WNT signaling pathway. However, the exact mechanism by which these factors exert their effects on hematopoietic stem cells remained unknown.
Beginning with the zebrafish model system, investigators showed that PGE2 directly increased WNT pathway activity within embryonic blood stem cells, leading to the formation of greater numbers of these stem cells. Exploring the underlying mechanisms, the researchers found that PGE2 helps stabilize an important component of the WNT pathway. In addition to demonstrating the importance of these factors to embryonic blood stem cell development, the scientists investigated a potential role for PEG2 and the WNT pathway in adult animals. By studying zebrafish whose blood stem cells had been destroyed by irradiation, the researchers discovered that these factors also work together to promote regeneration of new blood stem cells in adult fish. Further studies revealed that PGE2 and WNT work together to promote formation of embryonic and adult blood stem cells in mice—evidence that these pathways also interact in mammals. Beyond blood cells, the PGE2/WNT interaction was also shown to be required for liver regeneration in both fish and mice. These results illuminate PGE2 and the WNT pathway as powerful regulators of cellular regeneration in the body. Future research efforts will delineate the feasibility of delivering appropriate levels of PGE2 to damaged tissues to promote WNT-dependent cellular regeneration in a precise and controlled manner to preempt further injury and restore health.
Goessling W, North TE, Loewer S, Lord AM, Lee S, Stoick-Cooper CL, Weidinger G, Puder M, Daley GQ, Moon RT, and Zon LI: Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell 136: 1136-1147, 2009.