Laboratorio de Hematobiología, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional (IPN), México, D.F., México.
Eur J Haematol. 2011 Oct;87(4):312-22. doi: 10.1111/j.1600-0609.2011.01657.x. Epub 2011 Jul 26.
Hematopoietic stem cells (HSC) are defined by their cardinal properties, such as sustained proliferation, multilineage differentiation, and self-renewal, which give rise to a hierarchy of progenitor populations with more restricted potential lineage, ultimately leading to the production of all types of mature blood cells. HSC are anchored by cell adhesion molecules to their specific microenvironment, thus regulating their cell cycle, while cell migration is essentially required for seeding the HSC of the fetal bone marrow (BM) during development as well as in adult BM homeostasis. The dystrophin-associated protein complex (DAPC) is a large group of membrane-associated proteins linking the cytoskeleton to the extracellular matrix and exhibiting scaffolding, adhesion, and signaling roles in muscle and non-muscle cells including mature blood cells. Because adhesion and migration are mechanisms that influence the fate of the HSC, we explored the presence and the feasible role of DAPC. In this study, we characterized the pattern expression by immunoblot technique and, by confocal microscopy analysis, the cellular distribution of dystrophin and utrophin gene products, and the dystrophin-associated proteins (α-, β-dystroglycan, α-syntrophin, α-dystrobrevin) in relation to actin filaments in freshly isolated CD34+ cells from umbilical cord blood. Immunoprecipitation assays demonstrated the presence of Dp71d/Dp71Δ110m ∼DAPC and Up400/Up140∼DAPC. The subcellular distribution of the two DAPC in actin-based structures suggests their dynamic participation in adhesion and cell migration. In addition, the particular protein pattern expression found in hematopoietic stem/progenitor cells might be indicative of their feasible participation during differentiation.
造血干细胞（HSC）的定义特征包括持续增殖、多谱系分化和自我更新，这些特征赋予了其更有限的潜在谱系祖细胞群体的层次结构，最终导致所有类型成熟血细胞的产生。HSC 通过细胞粘附分子锚定在其特定的微环境中，从而调节其细胞周期，而细胞迁移对于在发育过程中以及在成人 BM 稳态中播种胎儿骨髓（BM）中的 HSC 是必不可少的。dystrophin 相关蛋白复合物（DAPC）是一大组膜相关蛋白，将细胞骨架与细胞外基质连接起来，并在肌肉和非肌肉细胞（包括成熟血细胞）中发挥支架、粘附和信号作用。由于粘附和迁移是影响 HSC 命运的机制，我们探索了 DAPC 的存在及其可能的作用。在这项研究中，我们通过免疫印迹技术描述了模式表达，并通过共聚焦显微镜分析，研究了肌营养不良蛋白和 utrophin 基因产物以及 dystrophin 相关蛋白（α-、β-肌营养不良蛋白、α- 连接蛋白、α- 肌球蛋白结合蛋白）在新鲜分离的脐带血 CD34+细胞中与肌动蛋白丝的细胞分布。免疫沉淀分析表明存在 Dp71d/Dp71Δ110m～DAPC 和 Up400/Up140～DAPC。两种 DAPC 在肌动蛋白为基础的结构中的亚细胞分布表明它们动态参与了粘附和细胞迁移。此外，造血干细胞/祖细胞中发现的特定蛋白模式表达可能表明它们在分化过程中可能的参与。
