Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Blood. 2011 Aug 11;118(6):1544-8. doi: 10.1182/blood-2010-10-316232. Epub 2011 May 31.
Lymphoid-primed multipotent progenitors with down-regulated megakaryocyte-erythroid (MkE) potential are restricted to cells with high levels of cell-surface FLT3 expression, whereas HSCs and MkE progenitors lack detectable cell-surface FLT3. These findings are compatible with FLT3 cell-surface expression not being detectable in the fully multipotent stem/progenitor cell compartment in mice. If so, this process could be distinct from human hematopoiesis, in which FLT3 already is expressed in multipotent stem/progenitor cells. The expression pattern of Flt3 (mRNA) and FLT3 (protein) in multipotent progenitors is of considerable relevance for mouse models in which prognostically important Flt3 mutations are expressed under control of the endogenous mouse Flt3 promoter. Herein, we demonstrate that mouse Flt3 expression initiates in fully multipotent progenitors because in addition to lymphoid and granulocyte-monocyte progenitors, FLT3(-) Mk- and E-restricted downstream progenitors are also highly labeled when Flt3-Cre fate mapping is applied.
淋巴样前体细胞-多能祖细胞具有下调的巨核细胞-红细胞（MkE）潜能，仅限于具有高水平细胞表面 FLT3 表达的细胞，而 HSCs 和 MkE 祖细胞缺乏可检测到的细胞表面 FLT3。这些发现与在小鼠的完全多能干细胞/祖细胞区室中不能检测到 FLT3 细胞表面表达是一致的。如果是这样，这个过程可能与人类造血不同，在人类造血中，FLT3 已经在多能干细胞/祖细胞中表达。Flt3（mRNA）和 FLT3（蛋白质）在多能祖细胞中的表达模式对于表达内源性小鼠 Flt3 启动子控制下具有预后重要性的 Flt3 突变的小鼠模型具有重要意义。在此，我们证明小鼠 Flt3 表达始于完全多能祖细胞，因为除了淋巴样和粒细胞-单核细胞祖细胞外，当应用 Flt3-Cre 命运图谱时，FLT3(-)Mk- 和 E-受限的下游祖细胞也被高度标记。
