Heterogeneity of Flt3-Expressing Multipotent Progenitors in Mouse Bone Marrow

Abstract

Mechanisms of lymphoid and myeloid lineage choice by hemopoietic stem cells remain unclear. In this study we show that the multipotent progenitor (MPP) population, which is immediately downstream of hemopoietic stem cells, is heterogeneous and can be subdivided in terms of VCAM-1 expression. VCAM-1+ MPPs were fully capable of differentiating into both lymphoid and myeloid lineages. In contrast, VCAM-1− MPPs gave rise to lymphocytes predominately in vivo. T and B cell development from VCAM-1− MPPs was 1 wk faster than that from VCAM-1+ MPPs. Furthermore, VCAM-1+ MPPs gave rise to common myeloid progenitors and VCAM-1− MPPs in vivo, indicating that VCAM-1− MPPs are progenies of VCAM-1+ MPPs. VCAM-1− MPPs, in turn, developed into lymphoid lineage-restricted common lymphoid progenitors. These results establish a hierarchy of developmental relationship between MPP subsets and lymphoid and myeloid progenitors. In addition, VCAM-1+ MPPs may represent the branching point between the lymphoid and myeloid lineages.