Single-Nucleus Transcriptomic Profiling of Hippocampi from WT and VCP p.R159H Mutant Mice with SDC4 Perturbation
Valosin-containing protein (VCP) is a core regulator of protein homeostasis and cellular stress responses, and its mutations cause progressive cognitive impairment. We generated VCP p.R155H and p.R159H mutant mice, which develop cognitive deficits at 12 months of age. To dissect the early cellular and molecular mechanisms underlying VCP mutation-driven cognitive dysfunction, we performed two batches of single-nucleus transcriptomic profiling using mouse hippocampal tissues.The first batch sequenced hippocampi from 12-month-old VCP p.R159H mutant mice and age-matched littermate controls. The second batch served for functional validation: we knocked down SDC4 in hippocampal astrocytes of 10-month-old VCP p.R159H mutant mice via AAV delivery and collected hippocampal tissues two months post-injection for single-nucleus sequencing. This dataset evaluates whether SDC4 knockdown corrects aberrant cellular states, thereby revealing the molecular mechanism through which SDC4 targeting rescues VCP mutation-induced cognitive impairment.