近日，美国麻省理工学院王潇等研究人员合作绘制出分子分辨率的小鼠中枢神经系统空间图谱。这一研究成果于2023年9月27日在线发表在国际学术期刊《自然》上。

研究人员使用STARmap PLUS这种原位测序方法，以194×194×345nm³的体素大小绘制了1022个基因的三维图谱，这在成年小鼠大脑和脊髓中绘制了109万个高质量细胞。研究人员开发了计算方案，通过单细胞基因表达对230种分子细胞类型进行分割、聚类和注释，并通过空间微环境基因表达对106个分子组织区域进行分割、聚类和注释。通过对分子细胞类型和分子组织区域的联合分析，研究人员建立了系统的分子空间细胞类型命名法，并识别了在已建立的脑解剖学中尚未定义的组织结构。

为了创建全转录组空间图谱，研究人员将STARmap PLUS测量结果与已发表的单细胞RNA测序图谱整合，推算出了11844个基因的单细胞表达谱。最后，研究人员描述了全脑转基因递送工具AAV-PHP.eB的病毒嗜性。这个注释数据集提供了一个单细胞资源，它整合了分子空间图谱、大脑解剖学和哺乳动物中枢神经系统遗传操作的可及性。

据介绍，以单细胞分辨率绘制三维空间的分子细胞类型图，对于说明大脑解剖和功能的分子基础至关重要。单细胞RNA测序分析了小鼠大脑中的分子细胞类型，但无法捕捉它们的空间组织。

附：英文原文

Title: Spatial atlas of the mouse central nervous system at molecular resolution

Author: Shi, Hailing, He, Yichun, Zhou, Yiming, Huang, Jiahao, Maher, Kamal, Wang, Brandon, Tang, Zefang, Luo, Shuchen, Tan, Peng, Wu, Morgan, Lin, Zuwan, Ren, Jingyi, Thapa, Yaman, Tang, Xin, Chan, Ken Y., Deverman, Benjamin E., Shen, Hao, Liu, Albert, Liu, Jia, Wang, Xiao

Issue&Volume: 2023-09-27

Abstract: Spatially charting molecular cell types at single-cell resolution across the 3D volume is critical for illustrating the molecular basis of brain anatomy and functions. Single-cell RNA sequencing has profiled molecular cell types in the mouse brain1,2, but cannot capture their spatial organization. Here we used an in situ sequencing method, STARmap PLUS3,4, to profile 1,022 genes in 3D at a voxel size of 194×194×345nm3, mapping 1.09 million high-quality cells across the adult mouse brain and spinal cord. We developed computational pipelines to segment, cluster and annotate 230 molecular cell types by single-cell gene expression and 106 molecular tissue regions by spatial niche gene expression. Joint analysis of molecular cell types and molecular tissue regions enabled a systematic molecular spatial cell-type nomenclature and identification of tissue architectures that were undefined in established brain anatomy. To create a transcriptome-wide spatial atlas, we integrated STARmap PLUS measurements with a published single-cell RNA-sequencing atlas1, imputing single-cell expression profiles of 11,844 genes. Finally, we delineated viral tropisms of a brain-wide transgene delivery tool, AAV-PHP.eB5,6. Together, this annotated dataset provides a single-cell resource that integrates the molecular spatial atlas, brain anatomy and the accessibility to genetic manipulation of the mammalian central nervous system.

DOI: 10.1038/s41586-023-06569-5

Source: https://www.nature.com/articles/s41586-023-06569-5

期刊信息

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