兴奋性毒性应激下小鼠脑中的 Cd47 缺失
Cd47 deficiency in mouse brain under excitotoxic stress
对野生型与 Cd47 敲除小鼠海马开展单核 RNA 测序，发现 Cd47 缺失使转录组向轻度兴奋性毒性应激状态偏移。研究用红藻氨酸（KA）按惊厥剂量 25 mg/kg 与亚惊厥剂量 3 mg/kg 处理小鼠，并将细胞类型注释与 WGCNA 结合，识别出随基因型和 KA 暴露而共表达结构不同的神经元与胶质基因模块，其中部分模块仅在 Cd47 缺陷细胞中随 KA 变化，富集于翻译、生物能量与突触相关基因集。用 Wasserstein 距离比较全转录组分布，在全部十五组两两比较中，溶媒处理的 KO 细胞最接近暴露于 KA3 的 WT 细胞。
来源：PLOS Computational Biology · journals.plos.org
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. Montine
CD47, 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.