Understanding the contribution of different macrophage populations to brain metastasis

Resumen del póster presentado al European Developmental Biology Congress (EDBC), celebrado en Alicante del 23 al 26 de octubre de 2019.Microglia, tissue-resident macrophages of the CNS, play key roles in brain homeostasis and disease. Inflammatory activation of microglia upon brain damage is considered a pathological hallmark and an important mechanism driving neurodegenerative diseases. Brain metastases can be conceptualized as a source of brain injury and as such, tumour cells promote microglial activation. In addition, recruited macrophages also contribute to the immune population of brain metastasis. Recent evidences suggest that the origins of the different macrophage populations influences their contribution to brain disease. While microglia derive from yolk-sac myeloid progenitors that colonize the brain during development, the major source of recruited macrophages is the bone marrow, however it has been classically difficult to distinguish both populations. Macrophages constitute critical regulators of tumour progression and responses to therapies, but their contribution to brain metastasis is poorly understood. To investigate this, we have established a brain colonization experimental model by injection of murine tumour cells into Cx3cr.1-CreERT2-YFP mice that can be used as a macrophage/microglia reporter model. Using this approach and recently described specific markers, we can observe that brain metastases are densely infiltrated by both microglia and recruited macrophages. We have isolated these specific populations by fluorescence activated cell sorting and perform RNA sequencing to identify differentially expressed genes and altered pathways that may regulate brain metastasis progression. In addition, we are performing single-cell RNA sequencing to help us understand the trajectory of cellular reprogramming of microglia and recruited macrophages in response to cancer cells.Peer reviewe