Figure 9.

Decoding the heterogeneity of MS with a reverse genetics approach. Analytical forward approach (blue arrows): The heterogeneity of the MS population is reflected by the heterogeneous course of MS and treatment responses. The hallmark of MS, WM brain lesions look similar on conventional MRI scans, but their histopathology is very different: characterized as active, inactive, chronic active and remyelinating/repairing lesions. This heterogeneity is most likely caused by the different cell types present in the lesions that is controlled by the heterogeneity of different networks and pathways activated within the cells and determined by some major hubs and molecular signatures. Biological hypothesis, reverse approach (red arrows): To decode this complexity, a reversed biological approach can be an alternative strategy. It can start from genetic regulation and molecular changes within individual cells that contribute to their fate. This will determine the evolution of lesions, and such complexity of lesion types will determine the individual MS brain and clinical outcomes. MS fate thus ultimately may depend on the interaction of singular cells.