Pertussis toxin-sensitive G proteins regulate lymphoid lineage specification in multipotent hematopoietic progenitors.
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. In this study, we show that lymphoid lineage specification occurs in MPPs before 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, 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.
Lai
Anne Y
AY
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Watanabe
Akiko
A
O'Brien
Tommy
T
Kondo
Motonari
M
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D019070:Cell Lineage / Q000187:drug effects*; D002478:Cells, Cultured; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D018398:Homeodomain Proteins; D019010:Vascular Cell Adhesion Molecule-1; C064658:RAG-1 protein; D037342:Pertussis Toxin; D020962:Heterotrimeric GTP-Binding Proteins