小柯机器人

空间基因组学实现对组织中克隆异质性的多模式研究
2021-12-19 23:52

美国哈佛大学Fei Chen、Jason D. Buenrostro等研究人员合作利用空间基因组学实现对组织中克隆异质性的多模式研究。相关论文于2021年12月15日在线发表在《自然》杂志上。

研究人员开发了slide-DNA-seq,一种从完整的组织切片中捕捉空间分辨率DNA序列的方法。研究人员证明这种方法准确地保留了局部肿瘤结构,并能从新发现不同的肿瘤克隆及其拷贝数的改变。然后,研究人员将slide-DNA-seq应用于小鼠转移模型和原发性人类癌症,揭示了克隆群体被限制在不同的空间区域。此外,通过与空间转录组学的整合,研究人员发现了与克隆特异性遗传畸变、局部肿瘤微环境或两者相关的不同基因组。总之,这种多模式的空间基因组学方法提供了一个多功能的平台,可以量化细胞内和细胞外的因素如何促进基因表达、蛋白质丰度和其他细胞表型。

据悉,细胞的状态和行为可以受到遗传和环境因素的影响。特别是,肿瘤的发展是由潜在的基因畸变以及肿瘤微环境的构成决定的。量化这些因素的贡献需要新的技术,从而准确测量基因组序列的空间位置和表型读数。

附:英文原文

Title: Spatial genomics enables multi-modal study of clonal heterogeneity in tissues

Author: Zhao, Tongtong, Chiang, Zachary D., Morriss, Julia W., LaFave, Lindsay M., Murray, Evan M., Del Priore, Isabella, Meli, Kevin, Lareau, Caleb A., Nadaf, Naeem M., Li, Jilong, Earl, Andrew S., Macosko, Evan Z., Jacks, Tyler, Buenrostro, Jason D., Chen, Fei

Issue&Volume: 2021-12-15

Abstract: The state and behaviour of a cell can be influenced by both genetic and environmental factors. In particular, tumour progression is determined by underlying genetic aberrations1,2,3,4 as well as the makeup of the tumour microenvironment5,6. Quantifying the contributions of these factors requires new technologies that can accurately measure the spatial location of genomic sequence together with phenotypic readouts. Here we developed slide-DNA-seq, a method for capturing spatially resolved DNA sequences from intact tissue sections. We demonstrate that this method accurately preserves local tumour architecture and enables the de novo discovery of distinct tumour clones and their copy number alterations. We then apply slide-DNA-seq to a mouse model of metastasis and a primary human cancer, revealing that clonal populations are confined to distinct spatial regions. Moreover, through integration with spatial transcriptomics, we uncover distinct sets of genes that are associated with clone-specific genetic aberrations, the local tumour microenvironment, or both. Together, this multi-modal spatial genomics approach provides a versatile platform for quantifying how cell-intrinsic and cell-extrinsic factors contribute to gene expression, protein abundance and other cellular phenotypes.

DOI: 10.1038/s41586-021-04217-4

Source: https://www.nature.com/articles/s41586-021-04217-4

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


本期文章:《自然》:Online/在线发表

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