Prominin-1-GFP knock-in mouse line: A novel source of fluorescent stem cells to monitor the history of the transplanted murine hematopoietic stem cells

这项研究计划的总体目的是开发一种新的敲入小鼠模型，该模型将在体内产生荧光造血干细胞（HSC），使我们能够监测移植HSC的归巢，命运和动员。为了建立这样一个系统，我们将使用pentaspan膜蛋白的一个新家族的第一个成员，和一个基于绿色荧光蛋白（GFP）的方法。小鼠红细胞生成素-1最初被鉴定为神经上皮干细胞的标志物，而其人直系同源物（也称为CD 133）被独立地显示在造血干细胞和祖细胞上表达。这种蛋白质的作用尚不清楚。尽管如此，鉴于人巨噬细胞蛋白-1/CD133的表达谱模拟鼠分子的表达谱，包括在几种其他发育早期细胞中的表达，巨噬细胞蛋白-1-GFP融合蛋白是理想的质膜标记物，用于通过光学成像方法在体内监测荧光移植的HSC的归巢、它们的增殖和分化能力以及最终它们在鼠移植模型中的动员。

The general purpose of this research program is to develop a novel knock-in mouse model that would generate in vivo-fluorescent hematopoietic stem cells (HSCs) allowing us to monitor the homing, fate and mobilization of transplanted HSCs. To establish such a system, we will use prominin-1, the first member of a new family of pentaspan membrane proteins and a green fluorescence protein (GFP)-based approach. Mouse prominin-1 was initially identified as a marker of neuroepithelial stem cells while its human orthologue (also referred to as CD133) was independently shown to be expressed on hematopoietic stem and progenitor cells. The role of this protein is still unknown. Nevertheless, given that the expression profile of human prominin-1/CD133 mimics that of the murine molecule including expression in several other developmentally early cells, the prominin-1-GFP fusion protein is an ideal plasma membrane marker to monitor in vivo by optical imaging methods the homing of the fluorescent transplanted HSCs, their proliferation and differentiation capacities and, finally their mobilization in murine transplantation models.