Stem Cell Biology and Transcriptomics of Human White Matter Diseases

Abstract

Multiple sclerosis (MS) is a common, debilitating, progressive and fatal neurological disease that targets myelinating oligodendrocytes. Although most likely driven by an autoimmune response, the effector mechanisms that cause inflammation and that lead to neurodegeneration are incompletely understood. Treatment options are limited and do not prevent the progressive phase. This talk will cover molecular, temporal and cellular diversity of glial cells in CNS development, and apply this perspective to understand what goes wrong in MS disease progression that: (1) causes inflammation in the brain, (2) death of neurons and brain shrinkage and (3) how to potentially enhance repair of lesions. In an effort to find biomarkers of disease progression and targets for new therapies, we have used transcriptomic approaches, stem cell models of oligodendrocyte disease that have highlighted a role for iron toxicity in cells of the oligodendrocyte lineage.