Brain Microenvironment Heterogeneity: Potential Value for Brain Tumors.

Uncovering the complexity of the microenvironment that emerges in brain disorders is key to identify potential vulnerabilities that might help challenging diseases affecting this organ. Recently, genomic and proteomic analyses, especially at the single cell level, have reported previously unrecognized diversity within brain cell types. The complexity of the brain microenvironment increases during disease partly due to the immune infiltration from the periphery that contributes to redefine the brain connectome by establishing a new crosstalk with resident brain cell types. Within the rewired brain ecosystem, glial cell subpopulations are emerging hubs modulating the dialogue between the Immune System and the Central Nervous System with important consequences in the progression of brain tumors and other disorders. Single cell technologies are crucial not only to define and track the origin of disease-associated cell types, but also to identify their molecular similarities and differences that might be linked to specific brain injuries. These altered molecular patterns derived from reprogramming the healthy brain into an injured organ, might provide a new generation of therapeutic targets to challenge highly prevalent and lethal brain disorders that remain incurable with unprecedented specificity and limited toxicities. In this perspective, we present the most relevant clinical and pre-clinical work regarding the characterization of the heterogeneity within different components of the microenvironment in the healthy and injured brain with a special interest on single cell analysis. Finally, we discuss how understanding the diversity of the brain microenvironment could be exploited for translational purposes, particularly in primary and secondary tumors affecting the brain.