Notch1 expression in early lymphopoiesis influences B versus T lineage determination

Notch receptors regulate fate decisions in many cells. One outcome of Notch signaling is differentiation of bipotential precursors into one cell type versus another. To investigate consequences of Notch1 expression in hematol ymphoid progenitors, mice were reconstituted with bone marrow (BM) transduc ed with retroviruses encoding a constitutively active form of Notch1. Altho ugh neither granulocyte or monocyte differentiation were appreciably affect ed, lymphopoiesis was dramatically altered. As early as 3 weeks following t ransplantation, mice receiving activated Notch1-transduced BM contained imm ature CD4(+)CD8(+) T cells in the BM and exhibited a simultaneous block in early B cell lymphopoiesis. These results suggest that Notch1 provides a ke y regulatory signal in determining T lymphoid versus B lymphoid lineage dec isions, possibly by influencing lineage commitment from a common lymphoid p rogenitor cell.