Heterogeneity of Flt3-expressing multipotent progenitors in mouse bone marrow.
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.
Lai
Anne Y
AY
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Lin
Simon M
SM
Kondo
Motonari
M
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology; D001854:Bone Marrow Cells / Q000166:cytology / Q000201:enzymology*; D002454:Cell Differentiation / Q000502:physiology; D008221:Lymphoid Tissue / Q000166:cytology / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000145:classification / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology / Q000201:enzymology; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D051941:fms-Like Tyrosine Kinase 3 / Q000096:biosynthesis* / Q000235:genetics
D019010:Vascular Cell Adhesion Molecule-1; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3