A Binary Cre Transgenic Approach Dissects Microglia and CNS Border-Associated Macrophages

The developmental and molecular heterogeneity of tissue macrophages is unravelling, as are theft diverse contributions to physiology and pathophysiology. Moreover, also given tissues harbor macrophages in discrete anatomic locations. Functional contributions of specific cell populations can in mice be dissected using Cre recombinase-mediated mutagenesis. However, single promoter-based Cre models show limited specificity for cell types. Focusing on macrophages in the brain, we establish here a binary transgenic system involving complementation-competent NCre and CCre fragments whose expression is driven by distinct promoters: Sall1(ncre): Cx3cr1(ccre) mice specifically target parenchymal microglia and compound transgenic Lyve1(ccre): Cx3cr1(ccre) animals target vasculature-associated macrophages, in the brain, as well as other tissues. We imaged the respective cell populations and retrieved their specific translatomes using the RiboTag in order to define them and analyze their differential responses to a challenge. Collectively, we establish the value of binary transgenesis to dissect tissue macrophage compartments and their functions.

Automated summary

Research has revealed the developmental and molecular heterogeneity of tissue macrophages, as well as their diverse roles in physiology and pathophysiology. By establishing a binary transgenic system in the brain, specific populations of macrophages, such as parenchymal microglia and vasculature-associated macrophages, can be targeted and analyzed for their differential responses to challenges using a method called RiboTag. This study demonstrates the value of binary transgenesis in dissecting tissue macrophage compartments and understanding their functions.