小柯机器人

美国纽约大学格罗斯曼医学院Shane A. Liddelow、Paul W. Frazel研究小组取得一项新突破。他们的研究利用小鼠和人类纵向scRNA-seq分析优化了小鼠星形胶质细胞快速分化的方法。2023年9月11日出版的《自然-神经科学》发表了这项成果。

研究人员使用单细胞/单核RNA测序（scRNA-seq/snRNA-seq）分析了小鼠胚胎和人诱导多能干细胞在巨胶质细胞分化过程中超过298,000个细胞和细胞核。研究通过计算鉴定了参与两个物种中神经胶质细胞命运规范的候选基因，并报告星形胶质细胞表面标志物在分化细胞中的异质表达。然后，研究人员使用转录组学数据来优化先前小鼠星形胶质细胞的分化方案，从而减少了整体方案的长度和复杂性。最后，研究人员使用多组学、双单核（sn）RNA-seq/snATAC-seq分析来揭示介导神经胶质分化的潜在基因组调控位点。

这些数据集使未来优化神经胶质分化方案成为可能，并提供对人类神经胶质分化的见解。

据了解，巨胶质细胞（星形胶质细胞和少突胶质细胞）是中枢神经系统正常发育和发挥功能所必需的，但在大脑和脊髓发育过程中，关于它们的分化仍然存在许多问题。

附：英文原文

Title: Longitudinal scRNA-seq analysis in mouse and human informs optimization of rapid mouse astrocyte differentiation protocols

Author: Frazel, Paul W., Labib, David, Fisher, Theodore, Brosh, Ran, Pirianian, Nicolette, Marchildon, Anne, Boeke, Jef D., Fossati, Valentina, Liddelow, Shane A.

Issue&Volume: 2023-09-11

Abstract: 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.

DOI: 10.1038/s41593-023-01424-2

Source: https://www.nature.com/articles/s41593-023-01424-2

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex