Hematopoietic stem cells (HSCs) are capable of both self-renewal and differentiation to maintain the entire blood/immune system throughout life. Oguro laboratory focuses on understanding how HSCs proliferate and mobilize in response to acute hematopoietic demands in mice and humans. Deciphering the molecular signals that allow HSCs to expand in vivo will be instructive for the development of clinical approaches to promote hematopoietic regeneration, such as after transplantation or blood loss, to increase the efficiency of collecting mobilized HSCs for transplantation, and to expand HSCs ex vivo. We are also seeking to understand how normal mechanisms that regulate HSC proliferation and mobilization in response to acute hematopoietic demands are exploited during the development and progression of hematopoietic malignancies, especially clonal hematopoiesis during aging.
Our parallel research objective is to generate long-term engraftable HSCs from hiPSCs by mimicking natural HSC development using a transgene-free and xeno-free method. This has the potential to provide a virtually unlimited supply of autologous HSCs for clinical transplantation to improve patient outcomes, and also offers diverse improved approaches for gene therapy, drug discovery, disease modeling, and in vitro modeling of human hematopoietic development.