State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China.
State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Cell Stem Cell. 2021 Jun 3;28(6):1160-1176.e7. doi: 10.1016/j.stem.2021.01.007. Epub 2021 Feb 9.
The use of the dual recombinase-mediated intersectional genetic approach involving Cre-loxP and Dre-rox has significantly enhanced the precision of in vivo lineage tracing, as well as gene manipulation. However, this approach is limited by the small number of Dre recombinase driver constructs available. Here, we developed more than 70 new intersectional drivers to better target diverse cell lineages. To highlight their applicability, we used these new tools to study the in vivo adipogenic fate of perivascular progenitors, which revealed that PDGFRa but not PDGFRaPDGFRb perivascular cells are the endogenous progenitors of adult adipocytes. In addition to lineage tracing, we used members of this new suite of drivers to more specifically knock out genes in complex tissues, such as white adipocytes and lymphatic vessels, that heretofore cannot be selectively targeted by conventional Cre drivers alone. In summary, these new transgenic tools expand the intersectional genetic approach while enhancing its precision.
利用涉及 Cre-loxP 和 Dre-rox 的双重组酶介导的交叉遗传方法，显著提高了体内谱系追踪和基因操作的精确性。然而，这种方法受到可用的 Dre 重组酶驱动构建体数量的限制。在这里，我们开发了 70 多个新的交叉驱动子，以更好地针对不同的细胞谱系。为了突出它们的适用性，我们使用这些新工具研究了血管周祖细胞的体内成脂命运，结果表明 PDGFRa 而不是 PDGFRaPDGFRb 血管周细胞是成年脂肪细胞的内源性祖细胞。除了谱系追踪，我们还使用这个新工具套件中的成员更具体地敲除复杂组织中的基因，例如白色脂肪细胞和淋巴管，迄今为止，这些组织不能仅通过传统的 Cre 驱动子进行选择性靶向。总之，这些新的转基因工具扩展了交叉遗传方法，同时提高了其精确性。
