Quantitative and Systems Biology Graduate Program, School of Natural Sciences, University of California, Merced, CA 95343, USA.
Exp Hematol. 2013 Jan;41(1):3-16. doi: 10.1016/j.exphem.2012.09.006. Epub 2012 Sep 25.
Wingless and int (Wnt) proteins are secreted proteins that are important for regulating hematopoietic stem cell self-renewal and differentiation in the bone marrow microenvironment in mice. The mechanisms by which Wnt signaling regulates these hematopoietic cell fate decisions are not fully understood. Secreted Wnt antagonists, which are expressed in bone and bone marrow stromal cells, either bind to Wnt ligands directly or block Wnt receptors and co-receptors to halt Wnt-mediated signal transduction in both osteolineage and hematopoietic cell types. Secreted frizzled related proteins-1 and -2, Wnt inhibitory factor-1, Dickkopf-1, and Sclerostin are Wnt antagonists that influence hematopoietic cell fate decisions in the bone marrow niche. In this review, we compare and contrast the roles of these Wnt antagonists and their effects on hematopoietic development in mice, and also discuss the clinical significance of targeting Wnt antagonists within the context of hematopoietic disease.
无翅型和整合素（Wnt）蛋白是分泌蛋白，对于调节小鼠骨髓微环境中的造血干细胞自我更新和分化非常重要。Wnt 信号通路调节这些造血细胞命运决定的机制尚未完全阐明。在骨和骨髓基质细胞中表达的分泌型 Wnt 拮抗剂，或者直接与 Wnt 配体结合，或者阻断 Wnt 受体和共受体，从而阻止 Wnt 介导的信号转导，影响成骨谱系和造血细胞类型。分泌型卷曲相关蛋白-1 和 -2、Wnt 抑制因子-1、Dickkopf-1 和 Sclerostin 是影响骨髓龛中造血细胞命运决定的 Wnt 拮抗剂。在这篇综述中，我们比较和对比了这些 Wnt 拮抗剂的作用及其对小鼠造血发育的影响，并讨论了在造血疾病背景下靶向 Wnt 拮抗剂的临床意义。
