Modeling human-specific interlaminar astrocytes in the mouse cerebral cortex.
Modeling human-specific interlaminar astrocytes in the mouse cerebral cortex.
复制标题
小鼠大脑皮层中人类特异性层间星形胶质细胞的建模。
DOI：
10.1002/cne.24979
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Dunaevsky A
中科院分区：
文献类型：
--
作者：
Padmashri R;Ren B;Oldham B;Jung Y;Gough R;Dunaevsky A
星形胶质细胞是一种高度异质性的胶质细胞，是脑发育和内环境稳定的重要调节因子。星形胶质细胞群体的异质性是其功能多样性的基础。除了典型的哺乳动物星形胶质细胞结构外，人类大脑皮层在颗粒上层中还表现出层间星形胶质细胞的放射状分布。这些灵长类动物特有的层间星形胶质细胞位于浅层，并投射穿过大脑皮层多层的长突起。然而，由于缺乏可访问的实验模型，其功能特性及其在调节神经元回路中的作用仍不清楚。在这里，我们通过将从人诱导的多能干细胞分化的星形胶质细胞移植到小鼠皮质中，在人源化神经胶质嵌合小鼠中模拟人层间星形胶质细胞。该模型为理解神经元-胶质细胞相互作用及其在神经系统疾病中的改变提供了一个新的平台。我们将从hiPSC分化的RFP表达星形胶质细胞移植到免疫缺陷小鼠的皮质中。植入后9个月，浅层皮质中的人星形胶质细胞发育成层间星形胶质细胞，其模仿成人皮质的层间星形胶质细胞结构。这种嵌合小鼠模型将能够在体内研究人类特异性层间星形胶质细胞。
Astrocytes, a highly heterogeneous population of glial cells, serve as essential regulators of brain development and homeostasis. The heterogeneity of astrocyte populations underlies the diversity in their functions. In addition to the typical mammalian astrocyte architecture, the cerebral cortex of humans exhibits a radial distribution of interlaminar astrocytes in the supragranular layers. These primate‐specific interlaminar astrocytes are located in the superficial layer and project long processes traversing multiple layers of the cerebral cortex. However, due to the lack of accessible experimental models, their functional properties and their role in regulating neuronal circuits remain unclear. Here we modeled human interlaminar astrocytes in humanized glial chimeric mice by engrafting astrocytes differentiated from human‐induced pluripotent stem cells into the mouse cortex. This model provides a novel platform for understanding neuron‐glial interaction and its alterations in neurological diseases. We engrafted RFP‐expressing astrocytes differentiated from hiPSCs into the cortex of immunodeficient mice neonatally. Nine months post engraftment, the human astrocytes in the superficial cortex developed into interlaminar astrocytes that mimicked the interlaminar astrocytes architecture of the adult human cortex. This chimeric mouse model will enable the study of human‐specific interlaminar astrocytes in vivo.
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星形胶质细胞诱导的突触发生的分子机制。
影响因子：
5.7
作者：
Baldwin KT;Eroglu C
通讯作者：
Eroglu C
DOI：
10.1523/jneurosci.4707-08.2009
发表时间：
2009-03-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Oberheim NA;Takano T;Han X;He W;Lin JH;Wang F;Xu Q;Wyatt JD;Pilcher W;Ojemann JG;Ransom BR;Goldman SA;Nedergaard M
通讯作者：
Nedergaard M
影响因子：
23.9
作者：
Han, Xiaoning;Chen, Michael;Wang, Fushun;Windrem, Martha;Wang, Su;Shanz, Steven;Xu, Qiwu;Oberheim, Nancy Ann;Bekar, Lane;Betstadt, Sarah;Silva, Alcino J.;Takano, Takahiro;Goldman, Steven A.;Nedergaard, Maiken
通讯作者：
Nedergaard, Maiken
影响因子：
2.9
作者：
Hirabayashi, Y;Gotoh, Y
通讯作者：
Gotoh, Y
影响因子：
9
作者：
Jones, V. C.;Atkinson-Dell, R.;Mohamet, L.
通讯作者：
Mohamet, L.