美国癌症神经科学中心Deneen, Benjamin课题组的研究认为CD51描述了神经回路中功能不同的星形胶质细胞亚型。相关论文于2026年10月21日发表在《自然》杂志上。

星形胶质细胞执行多种促进脑生理功能的任务，这提示这些多样的星形胶质细胞作用可能由功能不同的亚型所实现。近期研究已鉴定出星形胶质细胞之间的分子多样性；然而，这种分子异质性是否反映具有不同功能的特化星形胶质细胞亚群仍不清楚。在此，基于此前的分子和功能研究，研究人员构建了CD51-FLP小鼠品系，使得能够在体内直接比较神经回路中CD51+与CD51−星形胶质细胞亚群的功能特性。研究表明，CD51+和CD51−星形胶质细胞在皮层和海马中均具有独特的形态学、生理学和发育特性。功能研究证明，CD51+星形胶质细胞选择性促进发育中皮层的突触形成以及海马的回路可塑性。机制上，研究人员发现CD51+星形胶质细胞通过glypican 6发挥作用以促进皮层中的突触形成，而CD51本身驱动海马的回路可塑性。将这些发现应用于脑损伤，研究人员发现CD51+星形胶质细胞通过增强突触重塑促进卒中后的功能恢复。总之，该研究鉴定出在发育中、成熟和损伤后的脑中表现出不同功能特性的特化星形胶质细胞亚群。

附：英文原文

Title: CD51 delineates functionally distinct astrocyte subtypes in neural circuits

Author: Woo, Junsung, Williamson, Michael R., Choi, Dongjoo, Akdemir, Ekin, Zlatkov, Thea, Yu, Kwanha, Kwon, Wookbong, Maleki, Ehson, Ko, Yeunjung, Sanchez, Kaitlyn, Maleki, Hussein, Choi, Jong Min, Serin-Harmanci, Akdes, Deneen, Benjamin

Issue&Volume: 2026-10-21

Abstract: Astrocytes perform a diverse range of tasks that facilitate brain physiology, raising the possibility that these diverse astrocytic roles are enabled by functionally distinct subtypes1,2. Recent studies identified molecular diversity among astrocytes3; however, whether this molecular heterogeneity reflects specialized astrocyte subpopulations with distinct functions remains unclear. Here, on the basis of previous molecular and functional studies4, we generated a CD51-FLP mouse line that enables direct comparison of the functional properties between CD51+ and CD51 astrocyte subpopulations in neural circuits in vivo. We show that CD51+ and CD51 astrocytes have unique morphological, physiological and developmental properties in both the cortex and hippocampus. Functional studies demonstrate that CD51+ astrocytes selectively promote synapse formation in the developing cortex and circuit plasticity in the hippocampus. Mechanistically, we found that CD51+ astrocytes function through glypican 6 to promote synapse formation in the cortex, while CD51 itself drives circuit plasticity in the hippocampus. Applying these findings to brain injury, we found that CD51+ astrocytes promote functional recovery after stroke through enhanced synaptic remodelling. Taken together, our studies identify specialized astrocyte subpopulations that exhibit distinct functional properties in the developing, mature and injured brain.

DOI: 10.1038/s41586-026-11186-z

Source:https://www.nature.com/articles/s41586-026-11186-z