小柯机器人

美国加州理工学院Mitchell Guttman、Rustem F. Ismagilov等研究人员合作开发出scSPRITE技术，可用于高阶三维基因组组织的单细胞测量。2021年8月23日，国际知名学术期刊《自然—生物技术》在线发表了这一成果。

研究人员表示，尽管三维（3D）基因组组织是细胞核功能的核心，但它一直难以在单细胞水平上测量。

为了解决这个问题，研究人员开发了"单细胞分割池识别标签扩展的相互作用"（scSPRITE）。scSPRITE使用分割池条码来标记同一细胞核内的DNA片段及其三维空间排列。因为scSPRITE测量多向DNA接触，它在单个细胞内生成的地图比接近连接所能实现的分辨率更高。研究人员将scSPRITE应用于数以千计的小鼠胚胎干细胞，并检测了已知的基因组结构，包括染色体区域、活性和非活性区间、拓扑关联域（TAD）以及围绕各种核体组织的长程染色体间结构。

研究人员观察到这些结构在整个群体中表现出不同程度的异质性，其中TAD代表了跨细胞的基因组组织动态单位。研究人员认为scSPRITE将成为研究异质群体内基因组结构的一个重要工具。

附：英文原文

Title: Single-cell measurement of higher-order 3D genome organization with scSPRITE

Author: Arrastia, Mary V., Jachowicz, Joanna W., Ollikainen, Noah, Curtis, Matthew S., Lai, Charlotte, Quinodoz, Sofia A., Selck, David A., Ismagilov, Rustem F., Guttman, Mitchell

Issue&Volume: 2021-08-23

Abstract: Although three-dimensional (3D) genome organization is central to many aspects of nuclear function, it has been difficult to measure at the single-cell level. To address this, we developed ‘single-cell split-pool recognition of interactions by tag extension’ (scSPRITE). scSPRITE uses split-and-pool barcoding to tag DNA fragments in the same nucleus and their 3D spatial arrangement. Because scSPRITE measures multiway DNA contacts, it generates higher-resolution maps within an individual cell than can be achieved by proximity ligation. We applied scSPRITE to thousands of mouse embryonic stem cells and detected known genome structures, including chromosome territories, active and inactive compartments, and topologically associating domains (TADs) as well as long-range inter-chromosomal structures organized around various nuclear bodies. We observe that these structures exhibit different levels of heterogeneity across the population, with TADs representing dynamic units of genome organization across cells. We expect that scSPRITE will be a critical tool for studying genome structure within heterogeneous populations.

DOI: 10.1038/s41587-021-00998-1

Source: https://www.nature.com/articles/s41587-021-00998-1

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex