Reconstruction of cell spatial organization from single-cell RNA sequencing data based on ligand-receptor mediated self-assembly.

Reconstruction of cell spatial organization from single-cell RNA sequencing data based on ligand-receptor mediated self-assembly.
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基于配体-受体介导的自组装的单细胞RNA测序数据重建细胞空间组织

DOI:
10.1038/s41422-020-0353-2
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发表时间:
2020-09
期刊:
影响因子:
44.1
通讯作者:
Zhang Z
Zhang Z
中科院分区:
生物学1区
文献类型:
--
作者:
Ren X;Zhong G;Zhang Q;Zhang L;Sun Y;Zhang Z

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单细胞RNA测序(scRNA-seq)通过提供前所未有的细胞和分子通量,彻底改变了转录组学研究,但在组织分离过程中,单个细胞的空间信息丢失了。虽然基于成像的技术,如原位测序显示出巨大的前景,但技术上的困难目前限制了它们的广泛使用。在这里,我们假设细胞空间组织本质上是由细胞身份编码的,并且可以至少部分地通过配体-受体相互作用来重建,并且我们提出了CSOmap,一个从scRNA-seq中推断细胞相互作用从头开始的计算工具。我们发现CSOmap可以成功地再现人类和小鼠多器官的空间组织,包括伪空间中多种癌症的肿瘤微环境,并揭示细胞相互作用的分子决定因素。此外,CSOmap很容易模拟基因或细胞类型的扰动,以获得新的生物学见解,特别是免疫细胞如何在肿瘤微环境中相互作用。CSOmap是一种广泛适用的工具,可以根据不同系统中各种组织的scRNA-seq数据来询问细胞组织。
Single-cell RNA sequencing (scRNA-seq) has revolutionized transcriptomic studies by providing unprecedented cellular and molecular throughputs, but spatial information of individual cells is lost during tissue dissociation. While imaging-based technologies such as in situ sequencing show great promise, technical difficulties currently limit their wide usage. Here we hypothesize that cellular spatial organization is inherently encoded by cell identity and can be reconstructed, at least in part, by ligand-receptor interactions, and we present CSOmap, a computational tool to infer cellular interaction de novo from scRNA-seq. We show that CSOmap can successfully recapitulate the spatial organization of multiple organs of human and mouse including tumor microenvironments for multiple cancers in pseudo-space, and reveal molecular determinants of cellular interactions. Further, CSOmap readily simulates perturbation of genes or cell types to gain novel biological insights, especially into how immune cells interact in the tumor microenvironment. CSOmap can be a widely applicable tool to interrogate cellular organizations based on scRNA-seq data for various tissues in diverse systems.
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