美国麻省理工学院Fei Chen等研究人员合作利用原位基因组测序技术解析出完整生物样品中的DNA序列和结构。这一研究成果于2020年12月31日在线发表在国际学术期刊《科学》上。

研究人员报道了原位基因组测序（IGS），这是一种同时对完整生物样品中的基因组进行测序和成像的方法。研究人员将IGS应用于人类成纤维细胞和早期小鼠胚胎，并在空间上将成千上万个基因组位点定位在单个核中。使用这些数据，研究人员表征了不同胚胎阶段的基因组结构中父母特异性的变化，并揭示了受精卵中的单细胞染色质结构域，以及未发现的全局染色体定位在各个胚胎中的表观遗传记忆。

这些结果证明了原位基因组测序如何直接将序列和结构从单碱基对到整个生物的不同长度尺度连接起来。

据悉，了解基因组的组织需要整合DNA序列和3D空间信息，但是，现有的全基因组方法缺乏碱基对序列解析或直接的空间定位。

附：英文原文

Title: In situ genome sequencing resolves DNA sequence and structure in intact biological samples

Author: Andrew C. Payne, Zachary D. Chiang, Paul L. Reginato, Sarah M. Mangiameli, Evan M. Murray, Chun-Chen Yao, Styliani Markoulaki, Andrew S. Earl, Ajay S. Labade, Rudolf Jaenisch, George M. Church, Edward S. Boyden, Jason D. Buenrostro, Fei Chen

Issue&Volume: 2020/12/31

Abstract: Understanding genome organization requires integration of DNA sequence and 3D spatial context, however, existing genome-wide methods lack either base-pair sequence resolution or direct spatial localization. Here, we describe in situ genome sequencing (IGS), a method for simultaneously sequencing and imaging genomes within intact biological samples. We applied IGS to human fibroblasts and early mouse embryos, spatially localizing thousands of genomic loci in individual nuclei. Using these data, we characterized parent-specific changes in genome structure across embryonic stages, revealed single-cell chromatin domains in zygotes, and uncovered epigenetic memory of global chromosome positioning within individual embryos. These results demonstrate how in situ genome sequencing can directly connect sequence and structure across length scales from single base pairs to whole organisms.

DOI: 10.1126/science.aay3446

Source: https://science.sciencemag.org/content/early/2020/12/29/science.aay3446