by Mehrdad Kiamari, Amalia Perna, Matteo Santoro, Abdel El Ariss, Eloise Berson, Jing Zhao, Chandresh R. Gajera, Edward J. Fox, Kathleen S. Montine, Nima Aghaeepour, Thomas J. MontineCD47, a transmembrane protein with well-established immune and neurodevelopmental roles, was recently identified as an abundant presynaptic protein in humans, non-human primates, and mice. To investigate how Cd47 influences neuronal stress and injury, we performed single-nucleus RNA sequencing of hippocampi from wild-type (WT) and Cd47 knockout (KO) mice exposed to kainic acid (KA) at convulsive (KA25; 25 mg/kg) or subconvulsive (KA3; 3 mg/kg) doses. Integrating cell-type annotations with Weighted Gene Co-expression Network Analysis (WGCNA) revealed distinct neuronal and glial gene modules whose co-expression structure differed by genotype and by KA exposure. Notably, certain modules showed KA-associated changes in co-expression structure only in Cd47-deficient cells. Enrichment analyses of these modules highlighted translational, bioenergetic, and synaptic gene sets. Comparing transcriptome-wide distributions using Wasserstein distance demonstrated that vehicle-treated KO cells most closely resembled WT cells exposed to KA3, of all fifteen pairwise comparisons. These findings suggest that Cd47 loss shifts the hippocampal transcriptome toward a state resembling mild excitotoxic stress, implicating Cd47 as a candidate regulator of neuronal stress adaptation and providing a hypothesis for testing that role.