Single-nulceus RNA sequencing of human-induced neuron and astrocytes treated with cell-secreted amyloid beta peptides

In this work, we investigated the early effects of Aβ peptides accumulation on gene expression profiles of human-induced neurons (hiNs). Using single-cell RNA sequencing, we show that cell-secreted Aβ up-regulates the expression of several synaptic-related genes and down-regulates the expression of genes associated with metabolic stress mainly in glutamatergic neurons and to a lesser degree in GABAergic neurons and astrocytes. These neuronal alterations correlate with activation of SEMA5, EPHA and NECTIN signaling pathways, which are important regulators of synaptic plasticity. Altogether, our findings indicate that slight elevations in Aβ concentrations are sufficient to elicit transcriptional changes in human neurons that can contribute to early alterations on neural network activity. Count table showing the number of counts per nucleus in 6-week-old human-induced neurons and astrocytes treated with conditioned media from CHO cell lines overexpressing the human APP695 (CHO-APPWT) or the London mutated APP695 (CHO-APPV717L) (Guillot-Sestier et al., 2012) or non-conditioned medium (Blank/control) . Metadata file associated with count table.本研究探讨了β淀粉样蛋白（Aβ）肽积累对诱导性人神经元（human-induced neurons，hiNs）基因表达谱的早期影响。借助单细胞RNA测序（single-cell RNA sequencing）技术，我们发现细胞分泌的Aβ可上调多条突触相关基因的表达，并下调与代谢应激相关的基因表达，该调控效应主要见于谷氨酸能神经元，在γ-氨基丁酸能神经元与星形胶质细胞中程度较轻。上述神经元改变与SEMA5、EPHA及NECTIN信号通路的激活相关，这些通路均为突触可塑性的重要调控因子。综上，本研究结果表明，Aβ浓度的轻度升高足以诱导人类神经元发生转录改变，进而可能促成神经网络活动的早期异常。 本研究附带的计数表展示了经过表达人类APP695的中国仓鼠卵巢（CHO，Chinese Hamster Ovary）细胞系条件培养基（CHO-APPWT）、过表达伦敦突变型APP695的CHO细胞系条件培养基（CHO-APPV717L，Guillot-Sestier等，2012）或非条件培养基（空白/对照组）处理的6周龄诱导性人神经元及星形胶质细胞的每个细胞核计数结果。与该计数表配套的元数据文件。