小柯机器人

美国哈佛大学庄小威团队绘制出分子定义和空间解析的小鼠全脑细胞图谱。这一研究成果于2023年12月13日在线发表在国际学术期刊《自然》上。

研究人员使用多路复用误差校正荧光原位杂交技术对整个成年小鼠大脑约1000万个细胞中的1100多个基因进行了成像，并通过整合多路复用误差校正荧光原位杂交和单细胞 RNA测序数据，在全转录组规模上进行了空间分辨的单细胞表达谱分析。利用这种方法，研究人员在整个小鼠大脑中生成了一个全面的细胞图谱，其中包括5000多个转录不同的细胞集群，属于300多种主要细胞类型，具有很高的分子和空间分辨率。将该图谱注册到小鼠大脑共同坐标框架后，就可以对各个脑区的细胞类型组成和组织进行系统量化。研究人员进一步确定了以独特的细胞类型组成为特征的空间模块，以及以细胞渐变为特征的空间梯度。

最后，这种高分辨率的细胞空间图谱（每个细胞都有全转录组表达谱）使研究人员能够推断数百个细胞类型对之间的细胞类型特异性相互作用，并预测这些细胞-细胞相互作用的分子（配体-受体）基础和功能影响。这些结果为人们深入了解大脑的分子和细胞结构提供了丰富的信息，也为神经回路的功能研究及其在健康和疾病中的功能障碍奠定了基础。

据悉，在哺乳动物的大脑中，数百万到数十亿个细胞组成了复杂的相互作用网络，以实现各种功能。细胞的巨大多样性和错综复杂的组织结构阻碍了人们对大脑功能的分子和细胞基础的理解。空间分辨单细胞转录组学的最新进展使人们能够系统地绘制复杂组织（包括多个脑区）中分子定义的细胞类型的空间组织图谱。然而，目前还没有一个全面的全脑细胞图谱。

附：英文原文

Title: Molecularly defined and spatially resolved cell atlas of the whole mouse brain

Author: Zhang, Meng, Pan, Xingjie, Jung, Won, Halpern, Aaron R., Eichhorn, Stephen W., Lei, Zhiyun, Cohen, Limor, Smith, Kimberly A., Tasic, Bosiljka, Yao, Zizhen, Zeng, Hongkui, Zhuang, Xiaowei

Issue&Volume: 2023-12-13

Abstract: In mammalian brains, millions to billions of cells form complex interaction networks to enable a wide range of functions. The enormous diversity and intricate organization of cells have impeded our understanding of the molecular and cellular basis of brain function. Recent advances in spatially resolved single-cell transcriptomics have enabled systematic mapping of the spatial organization of molecularly defined cell types in complex tissues1,2,3, including several brain regions (for example, refs. 1,2,3,4,5,6,7,8,9,10,11). However, a comprehensive cell atlas of the whole brain is still missing. Here we imaged a panel of more than 1,100 genes in approximately 10 million cells across the entire adult mouse brains using multiplexed error-robust fluorescence in situ hybridization12 and performed spatially resolved, single-cell expression profiling at the whole-transcriptome scale by integrating multiplexed error-robust fluorescence in situ hybridization and single-cell RNA sequencing data. Using this approach, we generated a comprehensive cell atlas of more than 5,000 transcriptionally distinct cell clusters, belonging to more than 300 major cell types, in the whole mouse brain with high molecular and spatial resolution. Registration of this atlas to the mouse brain common coordinate framework allowed systematic quantifications of the cell-type composition and organization in individual brain regions. We further identified spatial modules characterized by distinct cell-type compositions and spatial gradients featuring gradual changes of cells. Finally, this high-resolution spatial map of cells, each with a transcriptome-wide expression profile, allowed us to infer cell-type-specific interactions between hundreds of cell-type pairs and predict molecular (ligand–receptor) basis and functional implications of these cell–cell interactions. These results provide rich insights into the molecular and cellular architecture of the brain and a foundation for functional investigations of neural circuits and their dysfunction in health and disease.

DOI: 10.1038/s41586-023-06808-9

Source: https://www.nature.com/articles/s41586-023-06808-9

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html