Ts-Biotag, a multimodal reporter of Tie2 expression, labels microglia in a model of neuro injury

Abstract

AbstractThe Ts-Biotag transgenic mouse reports the expression of receptor tyrosine kinase Tie2, a known marker of angiogenic states for both vascular endothelial cells and macrophages. We demonstrate Ts-Biotag labeling and Tie2 expression in a neural injury model to find the majority of labeling occurs in the myeloid derived and brain resident cell type, microglia. Additionally the ligand of Tie2, Ang1, is dynamically expressed, first in astrocytes then neural progenitor during wound signaling and healing. These results offer a Tie2 specific, in vivo view of a neuroimmune response to injury, suggesting a microglia/neural progenitor intercellular interaction guides recovery from a brain lesion.Graphical AbstractThe Ts-Biotag mouse reports expression of Tie2 for any imaging modality compatible with avidinated agents. Mice were given a transcranial cryo-injury and Ts-Biotag activity was followed for 7 days with MRI and histology, showing local and systemic Ts-Biotag labeling. Histology of WT and labeled bone marrow chimeras showed the protein Tie2 expressed in microglia, which assembled at the border of the lesion 1-2d post injury before invading by day 7. The main ligand of Tie2, Ang1, was first expressed systemically by astrocytes, then by neural progenitor cells proximal to and within the lesion. These results elucidate an axis of intercellular signaling involved in the resolution of inflammation and partial healing of a CNS injury.