Nature子刊:类器官细胞分型新技术
创作:orchid 审核:周旸 01月06日
  • 将流式细胞技术、蛋白翻译后修饰(PTM)信号检测、硫醇基反应原位标记系统联用,开发了类器官内单细胞信号网络分析的新方法;
  • 在鼠类的肠类器官中,对超过100万个单细胞中的28个PTM进行分析,可以区分干细胞、潘氏细胞、肠内分泌细胞、簇状细胞和杯状细胞等细胞类型,及其所处细胞状态;
  • 在结直肠癌类器官,新方法在单细胞水平描述了致癌基因突变、微环境对于肠道细胞状态的影响,揭示了多个致癌基因突变所影响的信号通路。
主编推荐语
周旸
蛋白翻译后修饰信号的检测可用于鉴定细胞类型和描述细胞状态。Nature Methods近期发表的研究开发了一种结合蛋白翻译后修饰信号检测、流式细胞技术的新方法,可以在单细胞水平分析类器官中的细胞类型和状态,并成功用该方法分析了正常、癌化肠道类器官中的细胞情况。该方法大大增强了对类器官内细胞功能和状态的分析能力,值得借鉴。
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Nature Methods [IF:30.822]

Cell-type-specific signaling networks in heterocellular organoids

异源类器官内细胞类型特异性信号网络分析

10.1038/s41592-020-0737-8

2020-02-17, Article

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Despite the widespread adoption of organoids as biomimetic tissue models, methods to comprehensively analyze cell-type-specific post-translational modification (PTM) signaling networks in organoids are absent. Here, we report multivariate single-cell analysis of such networks in organoids and organoid cocultures. Simultaneous analysis by mass cytometry of 28 PTMs in >1 million single cells derived from small intestinal organoids reveals cell-type- and cell-state-specific signaling networks in stem, Paneth, enteroendocrine, tuft and goblet cells, as well as enterocytes. Integrating single-cell PTM analysis with thiol-reactive organoid barcoding in situ (TOBis) enables high-throughput comparison of signaling networks between organoid cultures. Cell-type-specific PTM analysis of colorectal cancer organoid cocultures reveals that shApc, KrasG12D and Trp53R172H cell-autonomously mimic signaling states normally induced by stromal fibroblasts and macrophages. These results demonstrate how standard mass cytometry workflows can be modified to perform high-throughput multivariate cell-type-specific signaling analysis of healthy and cancerous organoids.

First Authors:
Xiao Qin

Correspondence Authors:
Christopher J Tape

All Authors:
Xiao Qin,Jahangir Sufi,Petra Vlckova,Pelagia Kyriakidou,Sophie E Acton,Vivian S W Li,Mark Nitz,Christopher J Tape

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