小柯机器人

美国索尔克生物研究所遗传学实验室Fred H. Gage课题组，报道了富胶质皮质类器官移植后人星形胶质细胞形态分化及功能成熟。该项研究成果发表在2024年2月28日出版的《自然—生物技术》上。

他们介绍了一种新的富含胶质细胞的皮质类器官模型，该模型显示出星形胶质细胞的加速发生。他们证明了在祖细胞亚群中诱导胶质源性开关能够快速衍生星形胶质细胞，星形胶质细胞在分化8-10周内占细胞群的25-31%。这些类器官的脑内移植可靠地产生了多种皮层神经元和人类星形胶质细胞的解剖亚类。空间转录组分析鉴定了类器官移植中星形胶质细胞不同亚类的层特异性表达模式。

使用体内急性神经炎症模型，他们确定了星形胶质细胞亚群，在细胞因子刺激下迅速激活促炎途径。此外，他们证明CD38信号在介导反应性星形胶质细胞的代谢，和线粒体应激中起着至关重要的作用。该模型为研究人类星形胶质细胞功能提供了一个强大的平台。

研究人员表示，星形胶质细胞是大脑中最丰富的胶质细胞类型，由于皮质胶质发生的延迟，在传统的皮质类器官模型中代表性不足。

附：英文原文

Title: Morphological diversification and functional maturation of human astrocytes in glia-enriched cortical organoid transplanted in mouse brain

Author: Wang, Meiyan, Zhang, Lei, Novak, Sammy Weiser, Yu, Jingting, Gallina, Iryna S., Xu, Lynne L., Lim, Christina K., Fernandes, Sarah, Shokhirev, Maxim N., Williams, April E., Saxena, Monisha D., Coorapati, Shashank, Parylak, Sarah L., Quintero, Cristian, Molina, Elsa, Andrade, Leonardo R., Manor, Uri, Gage, Fred H.

Issue&Volume: 2024-02-28

Abstract: Astrocytes, the most abundant glial cell type in the brain, are underrepresented in traditional cortical organoid models due to the delayed onset of cortical gliogenesis. Here we introduce a new glia-enriched cortical organoid model that exhibits accelerated astrogliogenesis. We demonstrated that induction of a gliogenic switch in a subset of progenitors enabled the rapid derivation of astroglial cells, which account for 25–31% of the cell population within 8–10weeks of differentiation. Intracerebral transplantation of these organoids reliably generated a diverse repertoire of cortical neurons and anatomical subclasses of human astrocytes. Spatial transcriptome profiling identified layer-specific expression patterns among distinct subclasses of astrocytes within organoid transplants. Using an in vivo acute neuroinflammation model, we identified a subpopulation of astrocytes that rapidly activates pro-inflammatory pathways upon cytokine stimulation. Additionally, we demonstrated that CD38 signaling has a crucial role in mediating metabolic and mitochondrial stress in reactive astrocytes. This model provides a robust platform for investigating human astrocyte function.

DOI: 10.1038/s41587-024-02157-8

Source: https://www.nature.com/articles/s41587-024-02157-8

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex