BCAP functions as a dynamic regulator of hematopoiesis and myeloid cell development

Abstract

Hematopoiesis governs the production of mature cells of the lymphoid, myeloid and erythroid lineages. This process occurs in the bone marrow of adult mammals, and generates these lineages throughout life. Furthermore, hematopoiesis is sensitive to multiple insults that drive demand for new hematopoietic cell differentiation, including infection, inflammation and myeloablation. These situations of demand alter hematopoietic differentiation to favor myeloid cell production, in a process known as emergency myelopoiesis. Both steady state hematopoiesis and emergency myelopoiesis are tightly regulated by a variety of signals in order to properly control the output of the different hematopoietic lineages. BCAP (B cell adaptor for PI-3 kinase) is a signaling adaptor protein expressed in hematopoietic cells, where it has a wide array of functions. Here we show that BCAP is expressed in the Hematopoietic Stem and Progenitor cells in the bone marrow, and acts as an inhibitor of myeloid cell development in both the steady state and during demand situations. Furthermore, we show that BCAP inhibits proliferation of the Long-Term Hematopoietic Stem cells, and therefore may regulate the quiescence and/or the self-renewal of this population in the BM. Overall, we have identified BCAP as a novel dynamic regulator of hematopoiesis and myeloid cell development.