1.
Speaker: Prof. Yoon-seong Kim(Rutgers University)
2. Topic:
Aging, a major risk factor for Parkinson’s Disease: Single-Cell Multiomic Approach of Human Midbrain
3. Date/time: 2023 Jun-29 / 1000-1130 (KST)
4. Place: Online (※ A Zoom address will be sent to your email and mobile
number before the lecture begins.)
5. Abstract
Age is the primary
risk factor for Parkinson’s disease (PD), but how aging changes the expression
and regulatory landscape of the brain remains unclear. Here, we present a
single-nuclei multiomic study profiling shared gene expression and chromatin
accessibility of young, aged, and PD post-mortem midbrain samples. Combined
multiomic analysis along a pseudopathogenesis trajectory reveals all glial cell
types are affected by age, but microglia and oligodendrocytes are further
altered in PD. We present evidence for a novel disease-associated
oligodendrocyte subtype and identify genes lost over the aging and disease
process, including CARNS1, that may predispose healthy cells to develop a
disease-associated phenotype. Surprisingly,
we found that chromatin accessibility is maintained without drastic changes
over aging or PD within the same cell types. Peak-gene association patterns,
however, are significantly altered during aging and PD, identifying
cell-type-specific chromosomal loci that contain PD-associated SNPs. We found that five ATAC peaks
containing 17 PD-associated SNPs exhibited differential association with
MAPT gene expression in disease-associated oligodendrocytes. Our study suggests
a previously undescribed role for oligodendrocytes in aging and PD pathogenesis.
