
Audrey Effenberger Thesis Defense: Oligodendrocyte progenitor heterogeneity in normal aging and neurodegeneration
Description
Tuesday, April 29, 2025
10–11 AM
46-3310 (Picower Seminar Room)
Zoom: https://mit.zoom.us/j/98400785840?pwd=az5ljtDhAzxy38pgmXxl6fcHV0rmtM.1
Title: Oligodendrocyte progenitor heterogeneity in normal aging and neurodegeneration
Abstract:
Oligodendrocyte progenitor cells (OPCs) are one of the four major glial cell types in the central nervous system (CNS). As their name suggests, OPCs are primarily defined by their capacity to differentiate into mature oligodendrocytes that form myelin sheaths around the axons in the CNS. However, OPCs continue to tile the adult CNS long after developmental myelination has concluded, and they contribute sparingly to oligodendrocyte turnover, suggesting that OPCs play important roles beyond OL replacement. To define the possible space of non-canonical OPC functions in the adult brain, I construct a transcriptomic atlas at single-cell resolution to reveal patterns of heterogeneity at local and global scales of anatomical organization. First, I characterize OPC heterogeneity in the pathologically normal human brain. I profile cells from prefrontal cortex, primary motor cortex, striatum, and ventral midbrain of 156 unique donor individuals. Across all sampled brain regions, I identify a subset of OPCs that is characterized by an angiogenic gene signature and hypothesize that these cells are perivascular OPCs that associate closely with the cerebrovascular endothelium. Furthermore, I find significant differences in gene expression between cortical and striatal OPCs which may correspond to functional specializations that support local neuronal function. Second, I profile OPCs from mouse motor cortex and dorsal striatum and perform a comparative analysis of human and mouse OPCs. Third, I characterize OPC transcriptomic dysregulation in Huntington’s disease (HD). In HD, I find that pvOPCs exhibit altered retinol metabolism and increased Wnt pathway activity. This aligns with known decreases in retinoic acid (RA) signaling in HD and suggests a potential role for pvOPCs in modulating vascular function via RA/Wnt signaling.