Submitted January 27, 2009
Accepted April 6, 2009
Pertussis toxin-sensitive G-proteins regulate lymphoid lineage specification in multipotent hematopoietic progenitors
Anne Y. Lai, Akiko Watanabe, Tommy O'Brien, and Motonari Kondo*
Department of Immunology, Duke University Medical Center, Durham, NC, United States
* Corresponding author; email: motonari.kondo{at}duke.edu.
Lymphoid and myeloid lineage segregation is a major developmental step during early hematopoiesis from hematopoietic stem cells. It is not clear, however, whether multipotent progenitors (MPPs) adopt a lymphoid or myeloid fate through stochastic mechanisms, or whether this process can be regulated by extracellular stimuli. Here we show that lymphoid lineage specification occurs in MPPs prior to lymphoid lineage priming, during which MPPs migrate from the proximal to the distal region relative to the endosteum of the bone marrow. Lymphoid specified MPPs have low myeloid differentiation potential in vivo, but potently differentiate into myeloid cells in vitro. When treated with pertussis toxin (PTX), an inhibitor of G-protein coupled receptor signaling, lymphoid specified MPPs regain in vivo myeloid potential and their localization is dispersed in the bone marrow. These results clearly demonstrate that specific microenvironments that favorably support lymphoid or myeloid lineage development exist at structurally distinct regions in the bone marrow.
