瑞典卡罗林斯卡学院Sten Linnarsson和Gioele La Manno研究团队合作揭示发育中的小鼠大脑的分子结构。相关论文发表在2021年7月28日出版的《自然》杂志上。

他们报告了原肠胚形成和出生之间胚胎小鼠大脑的综合单细胞转录组图谱。他们确定了近 800 种细胞状态，这些状态描述了大脑及其封闭膜的功能元件的发育程序，包括早期神经上皮、区域特异性次级组织器以及神经源性和胶质源性祖细胞。他们还使用原位 mRNA 测序来绘制关键发育基因的空间表达模式。将原位数据与他们的单细胞簇相结合，揭示了神经系统模式化过程中神经祖细胞的精确空间组织。

研究人员表示，哺乳动物大脑是通过由可扩散的形态发生素、细胞间相互作用和内在遗传程序产生的空间线索的复杂相互作用而进行发育，这些因素可能产生一千多种不同的细胞类型。对这个过程的完整理解需要在大脑发育的整个时空范围内对细胞状态进行系统表征。因此，单细胞 RNA 测序和空间转录组学揭示复杂组织的分子异质性的能力在神经系统中特别强大。以前的研究探索了特定大脑区域、整个成人大脑甚至整个胚胎的发育。

附：英文原文

Title: Molecular architecture of the developing mouse brain

Author: La Manno, Gioele, Siletti, Kimberly, Furlan, Alessandro, Gyllborg, Daniel, Vinsland, Elin, Mossi Albiach, Alejandro, Mattsson Langseth, Christoffer, Khven, Irina, Lederer, Alex R., Dratva, Lisa M., Johnsson, Anna, Nilsson, Mats, Lnnerberg, Peter, Linnarsson, Sten

Issue&Volume: 2021-07-28

Abstract: The mammalian brain develops through a complex interplay of spatial cues generated by diffusible morphogens, cell–cell interactions and intrinsic genetic programs that result in probably more than a thousand distinct cell types. A complete understanding of this process requires a systematic characterization of cell states over the entire spatiotemporal range of brain development. The ability of single-cell RNA sequencing and spatial transcriptomics to reveal the molecular heterogeneity of complex tissues has therefore been particularly powerful in the nervous system. Previous studies have explored development in specific brain regions1,2,3,4,5,6,7,8, the whole adult brain9 and even entire embryos10. Here we report a comprehensive single-cell transcriptomic atlas of the embryonic mouse brain between gastrulation and birth. We identified almost eight hundred cellular states that describe a developmental program for the functional elements of the brain and its enclosing membranes, including the early neuroepithelium, region-specific secondary organizers, and both neurogenic and gliogenic progenitors. We also used in situ mRNA sequencing to map the spatial expression patterns of key developmental genes. Integrating the in situ data with our single-cell clusters revealed the precise spatial organization of neural progenitors during the patterning of the nervous system.

DOI: 10.1038/s41586-021-03775-x

Source: https://www.nature.com/articles/s41586-021-03775-x