Study Uncovers Mosaic Loss of Chromosome Y in Human Microglia

By analyzing single-cell and single-nuclei RNA sequencing data, scientists from the University of British Columbia and Harvard Medical School have generated evidence of mosaic loss of chromosome Y (LOY) in human microglia, uncovering a potential role for the acquired structural mutation in neurodegenerative disorders. LOY is common in the leukocytes of aging men and is correlated with a number of age-related diseases, but the molecular basis of LOY in brain cells is poorly understood. To investigate, the researchers consolidated existing scRNA- and snRNA-seq datasets, which they used to assess the cell type-specific burden of LOY and its downstream impact on gene expression across five major brain cell types. As reported in Genome Research this week, the group finds that LOY is enriched in microglia, but rare in neurons, astrocytes, and oligodendrocytes. Differential gene expression analysis in microglia, meantime, revealed 172 autosomal genes, three X-linked genes, and 10 pseudo-autosomal genes associated with LOY. "We believe LOY in the microglia could represent an additional, understudied biological process that could alter microglia phenotypes and play a role in male-specific neurodegeneration," the study's authors write.