Single Cell Club presents: Single-cell expression QTL analyses of the human cerebellum reveal vulnerability of oligodendrocytes in essential tremor
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Speaker:
Charles-Etienne Castonguay, M. D., Ph. D.
R1 Neurologie, Institut Neurologique de Montr茅al
Irving Ludmer Psychiatry Research and Training Building
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搁茅蝉耻尘茅:
Essential tremor is a movement disorder characterized by an upper-limb postural and action tremor. It is one of the most common neurological disorders, affecting 1% of the worldwide population. Despite strong evidence for genetic factors driving the etiology of essential tremor, the underlying pathophysiology remains poorly understood. To understand the effects of genetic risk factors in essential tremor on the cerebellum, the brain region suspected to be affected by the disease, we built a population-scale single-cell atlas of the human cerebellar cortex comprised of over 1 million cells from 109 individuals. Using single-cell expression quantitative trait loci and Mendelian randomization, we show that essential tremor-associated variants in the BACE2 locus are causally linked to its downregulation in cerebellar oligodendrocytes. We highlight a genetically vulnerable population of BACE2-expressing immature oligodendrocytes, suggestive of demyelination. We also find dysfunctional processes affecting interactions between neuronal populations and oligodendrocytes in essential tremor. Our study suggests a crucial role for cerebellar oligodendrocytes in the pathogenesis of essential tremor.
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