Yuan Xiaodong, Li Wen, Liu Qing, Ou Ya, Li Jing, Yan Qi, Zhang Pingshu
Department of Neurology, Kailuan General Hospital Affiliated North China University of Science and Technology, 57 Xinhua East Road, Lubei District, Tangshan, 063000, Hebei, China.
Department of Neurology, Hebei Provincial Key Laboratory of Neurobiological Function, Tangshan, 063000, Hebei, China.
Cell Mol Neurobiol. 2024 Dec 11;45(1):5. doi: 10.1007/s10571-024-01524-y.
Adipose-derived stromal cells (ADSCs) are commonly used in regenerative medicine, but the genetic features of their development into neuronal cells are unknown. This study used single-cell RNA sequencing (scRNA-seq) to reveal gene expression changes during ADSCs to neuronal differentiation. Sequencing of the ADSCs group, the prei-1d group, and the induction 1 h, 3 h, 5 h, 6 h, and 8 h groups was performed using the BD Rhapsody platform. Sequence data were analyzed using t-SNE, Monocle2, GO, and KEGG algorithms. Results showed that a total of 38,453 cells were collected, which were divided into 0-13 clusters. Monocle2 structured analysis revealed that ADSCs were located at the beginning of the trajectory, and the cells after 5 h of induction were mainly distributed at the end of the trajectory in branches 1 and 2. Up-regulated differentially expressed genes (DEGs) at 5 h after induction enriched GO items including cellular protein metabolism, cell adhesion, endocytosis, and cell migration. KEGG analysis showed that induced 6 h and 8 h groups mainly enriched pathways were oxidative phosphorylation, glutathione metabolism, and expression of Parkinson's disease-related genes. In conclusion, two distinct cell state mechanisms stimulate ADSCs to develop into mature neurons. ADSCs induced for 5 h had developed into mature neurons. Later, the differentiated cells undergo degenerative changes associated with senescence.
脂肪来源的间充质干细胞（ADSCs）常用于再生医学，但其向神经元细胞分化过程中的基因特征尚不清楚。本研究采用单细胞RNA测序（scRNA-seq）来揭示ADSCs向神经元分化过程中的基因表达变化。使用BD Rhapsody平台对ADSCs组、诱导前1天组以及诱导1小时、3小时、5小时、6小时和8小时组进行测序。使用t-SNE、Monocle2、GO和KEGG算法对序列数据进行分析。结果显示，共收集到38453个细胞，分为0至13个簇。Monocle2结构分析表明，ADSCs位于轨迹的起始位置，诱导5小时后的细胞主要分布在轨迹末端的分支1和分支2中。诱导后5小时上调的差异表达基因（DEGs）富集了包括细胞蛋白质代谢、细胞粘附、内吞作用和细胞迁移等在内的GO条目。KEGG分析表明，诱导6小时和8小时组主要富集的通路是氧化磷酸化、谷胱甘肽代谢以及帕金森病相关基因的表达。总之，两种不同的细胞状态机制刺激ADSCs发育为成熟神经元。诱导5小时的ADSCs已发育为成熟神经元。随后，分化的细胞经历与衰老相关的退行性变化。
