生物
转录组
星形胶质细胞
细胞分化
计算生物学
胚胎干细胞
神经科学
诱导多能干细胞
电池类型
单细胞分析
细胞生物学
基因表达
细胞
基因
中枢神经系统
遗传学
作者
Paul W. Frazel,David Labib,T Fisher,Ran Brosh,Nicolette Pirjanian,Anne E Marchildon,Jef D. Boeke,Valentina Fossati,Shane A. Liddelow
标识
DOI:10.1038/s41593-023-01424-2
摘要
Macroglia (astrocytes and oligodendrocytes) are required for normal development and function of the central nervous system, yet many questions remain about their emergence during the development of the brain and spinal cord. Here we used single-cell/single-nucleus RNA sequencing (scRNA-seq/snRNA-seq) to analyze over 298,000 cells and nuclei during macroglia differentiation from mouse embryonic and human-induced pluripotent stem cells. We computationally identify candidate genes involved in the fate specification of glia in both species and report heterogeneous expression of astrocyte surface markers across differentiating cells. We then used our transcriptomic data to optimize a previous mouse astrocyte differentiation protocol, decreasing the overall protocol length and complexity. Finally, we used multi-omic, dual single-nuclei (sn)RNA-seq/snATAC-seq analysis to uncover potential genomic regulatory sites mediating glial differentiation. These datasets will enable future optimization of glial differentiation protocols and provide insight into human glial differentiation. The transcriptional program underlying the origin of glial cells is unclear. Here the authors leverage single-cell/single-nucleus transcriptional and chromatin accessibility profiling to identify candidate cell fate specification genes and optimize a rapid astrocyte differentiation protocol.
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