Lai Anne Y, Lin Simon M, Kondo Motonari
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
J Immunol. 2005 Oct 15;175(8):5016-23. doi: 10.4049/jimmunol.175.8.5016.
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.
造血干细胞选择淋巴样和髓样谱系的机制仍不清楚。在本研究中，我们表明，位于造血干细胞下游的多能祖细胞（MPP）群体是异质性的，可根据VCAM-1表达进行细分。VCAM-1(+) MPPs完全能够分化为淋巴样和髓样谱系。相比之下，VCAM-1(-) MPPs在体内主要产生淋巴细胞。VCAM-1(-) MPPs的T细胞和B细胞发育比VCAM-1(+) MPPs快1周。此外，VCAM-1(+) MPPs在体内产生普通髓样祖细胞和VCAM-1(-) MPPs，这表明VCAM-1(-) MPPs是VCAM-1(+) MPPs的后代。反过来，VCAM-1(-) MPPs发育为淋巴样谱系受限的普通淋巴样祖细胞。这些结果确立了MPP亚群与淋巴样和髓样祖细胞之间发育关系的层次结构。此外，VCAM-1(+) MPPs可能代表淋巴样和髓样谱系之间的分支点。
