Activity of human-specific Interlaminar Astrocytes in a Chimeric Mouse Model of Fragile X Syndrome.

Alexandria Anding, Baiyan Ren, Ragunathan Padmashri, Maria Burkovetskaya, Anna Dunaevsky
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Abstract

Astrocytes, a subtype of glial cells, have multiple roles in regulating neuronal development and homeostasis. In addition to the typical mammalian astrocytes, in the primate cortex interlaminar astrocytes are located in the superficial layer and project long processes traversing multiple layers of the cerebral cortex. Previously, we described a human stem cell based chimeric mouse model where interlaminar astrocytes develop. Here, we utilized this model to study the calcium signaling properties of interlaminar astrocytes. To determine how interlaminar astrocytes could contribute to neurodevelopmental disorders, we generated a chimeric mouse model for Fragile X syndrome. We report that FXS interlaminar astrocytes exhibit hyperexcitable calcium signaling and are associated with dendritic spines with increased turnover rate.

人类特异性层间星形细胞在脆性X综合征嵌合小鼠模型中的活性。
星形胶质细胞是神经胶质细胞的一种,在调节神经元发育和体内平衡中具有多种作用。除了典型的哺乳动物星形胶质细胞外,在灵长类动物皮层中,层间星形胶质细胞位于大脑皮层的浅层,并投射出穿越大脑皮层多层的长过程。先前,我们描述了一种基于人类干细胞的嵌合小鼠模型,其中层间星形胶质细胞发育。本研究利用该模型研究层间星形胶质细胞钙信号传导特性。为了确定层间星形细胞如何导致神经发育障碍,我们建立了一个脆性X综合征的嵌合小鼠模型。我们报道FXS层间星形胶质细胞表现出高兴奋的钙信号并导致树突棘动力学增加。
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