Sparse neuronal C4 elevation induces network-wide transcriptomic and lipid-droplet remodeling in the cortical microenvironment.

Sparse neuronal C4 overexpression in about 2% of prefrontal cortex neurons induces widespread transcriptomic and lipid-droplet remodeling in the cortical microenvironment.

• Why it matters: Understanding whether localized increases in C4 can influence broader brain tissue programs is crucial for elucidating mechanisms underlying neurological disorders like schizophrenia, where C4A is genetically linked to disease risk.
• What they did: The study used in utero electroporation to overexpress mouse C4 in a small neuronal subset and performed bulk RNA sequencing on microdissected prefrontal cortex, revealing broad gene expression changes despite sparse manipulation.
• The result: Findings show that localized C4 elevation is associated with remodeling of cholesterol biosynthesis, synaptic, vascular, immune, and stress pathways, including lipid droplet accumulation and non-cell-autonomous responses, expanding the understanding of C4’s role in cortical vulnerability.