Gene expression of brain cells from wild type and Gba flox/flox; Nestin-Cre mice. Gene expression of brain cells from wild type and Gba flox/flox; Nestin-Cre mice

To investigate neuronopathic Gaucher disease brain cell gene expression, we established Gba flox/flox; Nestin-Cre mice and performed scRNA sequencing of whole brain cells from these and wild type mice. Unbiased clustering analysis revealed that most remarkable change between wild type and Gba flox/flox; Nestin-Cre mice was the appearance of an activated microglia cluster, which exclusively expressed Tnf. Our further study elucidated the mechanism by which activated microglia and TNF contribute to Gaucher disease pathology. Overall design: Whole brain cells from 2-week-old wild type and Gba flox/flox; Nestin-Cre mice were analyed using scRNA sequencing.

为探究神经元病变型戈谢病的脑细胞基因表达特征，我们构建了Gba flox/flox; Nestin-Cre小鼠，并对该模型小鼠与野生型小鼠的全脑细胞开展了单细胞RNA测序（scRNA sequencing）。无偏聚类分析显示，野生型小鼠与Gba flox/flox; Nestin-Cre小鼠间最显著的差异为激活型小胶质细胞簇的出现，该细胞簇特异性表达肿瘤坏死因子（Tnf）。本研究后续进一步阐明了激活型小胶质细胞与肿瘤坏死因子在戈谢病病理进程中的作用机制。实验整体设计：选取2周龄野生型及Gba flox/flox; Nestin-Cre小鼠的全脑细胞，通过单细胞RNA测序完成分析。