小柯机器人

瑞典卡洛琳卡学院Jonas Frisén团队利用单细胞和空间转录组学揭示小鼠大脑中的克隆关系。这一研究成果于2022年2月24日在线发表于国际学术期刊《自然—神经科学》上。

研究人员利用单细胞和空间转录组学对小鼠大脑中的早期祖先进行体内条形码标记，用于同时剖析细胞表型和克隆关系。通过重建数以千计的克隆，研究人员在小鼠海马神经上皮细胞中发现了命运受限的祖细胞，并表明小胶质细胞来自少数原始骨髓前体，这些骨髓前体大规模扩张，产生广泛分散的后代。研究人员将空间转录组学与克隆条形码相结合，在密集标记的组织切片中分解出克隆相关细胞的迁移模式。这个方法能够在单个动物的单细胞和组织水平上对细胞表型和克隆关系进行高通量的密集重建，并为理解组织结构提供了一种综合方法。

据介绍，哺乳动物的大脑包含许多专门的细胞，它们从薄薄的神经上皮祖细胞发育而来。单细胞转录组学揭示了神经系统中数百种分子不同的细胞类型，但对成熟细胞类型和祖细胞之间的系谱关系却不甚了解。

附：英文原文

Title: Clonal relations in the mouse brain revealed by single-cell and spatial transcriptomics

Author: Ratz, Michael, von Berlin, Leonie, Larsson, Ludvig, Martin, Marcel, Westholm, Jakub Orzechowski, La Manno, Gioele, Lundeberg, Joakim, Frisn, Jonas

Issue&Volume: 2022-02-24

Abstract: The mammalian brain contains many specialized cells that develop from a thin sheet of neuroepithelial progenitor cells. Single-cell transcriptomics revealed hundreds of molecularly diverse cell types in the nervous system, but the lineage relationships between mature cell types and progenitor cells are not well understood. Here we show in vivo barcoding of early progenitors to simultaneously profile cell phenotypes and clonal relations in the mouse brain using single-cell and spatial transcriptomics. By reconstructing thousands of clones, we discovered fate-restricted progenitor cells in the mouse hippocampal neuroepithelium and show that microglia are derived from few primitive myeloid precursors that massively expand to generate widely dispersed progeny. We combined spatial transcriptomics with clonal barcoding and disentangled migration patterns of clonally related cells in densely labeled tissue sections. Our approach enables high-throughput dense reconstruction of cell phenotypes and clonal relations at the single-cell and tissue level in individual animals and provides an integrated approach for understanding tissue architecture. Ratz et al. present an easy-to-use method to barcode progenitor cells, enabling profiling of cell phenotypes and clonal relations using single-cell and spatial transcriptomics, providing an integrated approach for understanding brain architecture.

DOI: 10.1038/s41593-022-01011-x

Source: https://www.nature.com/articles/s41593-022-01011-x

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