小柯机器人

美国麻省理工学院和哈佛大学布罗德研究所Fei Chen和Jason D. Buenrostro共同合作，近期取得重要工作进展。他们研究开发了光选择性测序方法，一种显微镜引导的亚细胞分辨率基因组测量。相关研究成果2023年4月27日在线发表于《自然—方法学》上。

据介绍，在生物系统中，空间组织和功能是相互联系的。

研究人员提出了光选择性测序，这是一种在形态学不同区域进行基因组和表观基因组分析的新方法。从完整的生物样本开始，光选择性测序使用靶向照明来选择性地解锁光笼片段库，将基于测序的读数限制在显微镜识别的空间区域。研究人员通过测量小鼠大脑中荧光标记细胞类型的染色质可及性谱并与已发表的数据进行比较来验证光选择性测序。

此外，通过将光选择性测序与分解大量可及性谱的计算策略相结合，研究人员发现皮质中的少突胶质细胞祖细胞相对富集，而胼胝体中少突胶质祖细胞相对丰富。最后，研究人员利用亚细胞水平的光选择性测序来识别与细胞核外围定位相关的染色质特征。这些结果共同证明，光选择性测序是一个灵活和可推广的平台，用于探索空间结构与基因组和表观基因组特性的相互作用。

附：英文原文

Title: Photoselective sequencing: microscopically guided genomic measurements with subcellular resolution

Author: Mangiameli, Sarah M., Chen, Haiqi, Earl, Andrew S., Dobkin, Julie A., Lesman, Daniel, Buenrostro, Jason D., Chen, Fei

Issue&Volume: 2023-04-27

Abstract: In biological systems, spatial organization and function are interconnected. Here we present photoselective sequencing, a new method for genomic and epigenomic profiling within morphologically distinct regions. Starting with an intact biological specimen, photoselective sequencing uses targeted illumination to selectively unblock a photocaged fragment library, restricting the sequencing-based readout to microscopically identified spatial regions. We validate photoselective sequencing by measuring the chromatin accessibility profiles of fluorescently labeled cell types within the mouse brain and comparing with published data. Furthermore, by combining photoselective sequencing with a computational strategy for decomposing bulk accessibility profiles, we find that the oligodendrocyte-lineage-cell population is relatively enriched for oligodendrocyte-progenitor cells in the cortex versus the corpus callosum. Finally, we leverage photoselective sequencing at the subcellular scale to identify features of chromatin that are correlated with positioning at the nuclear periphery. These results collectively demonstrate that photoselective sequencing is a flexible and generalizable platform for exploring the interplay of spatial structures with genomic and epigenomic properties.

DOI: 10.1038/s41592-023-01845-8

Source: https://www.nature.com/articles/s41592-023-01845-8

Nature Methods：《自然—方法学》，创刊于2004年。隶属于施普林格·自然出版集团，最新IF：47.99
官方网址：https://www.nature.com/nmeth/
投稿链接：https://mts-nmeth.nature.com/cgi-bin/main.plex