美国加州大学旧金山分校Matthew F. Krummel课题组发展了一种利用光控空间编码进行实时单细胞空间转录组学研究的技术，称为ZipSeq。这一研究成果于2020年7月6日发表在《自然—方法学》上。

课题组人员开发了名为“ZipSeq”的方法，通过特定模式照明和光笼寡核苷酸将DNA编码（‘zipcodes') 标记到完整组织的活细胞上，为后续单细胞组学数据记录细胞位置信息，具有实时和动态选择模式的特点。

研究人员还利用ZipSeq对三个生物体系（体外伤口愈合、活淋巴结组织切片和活肿瘤微环境）的基因表达模式进行了映射。 在所有体系下，研究人员都发现了与组织结构相关联的新的基因表达新模式。在肿瘤微环境中，基因表达模式表明了骨髓和T细胞由外围向内的分化轨迹。ZipSeq的组合变体可以有效地缩放所定义区域的数量，从而为实时或微扰之后活组织基因表达模式的完整绘制提供了途径。

据介绍，空间转录组学技术需要同时获取单细胞转录组数据及其在多细胞生物中的三维空间位置信息。然而在活组织水平，将细胞位置与其单细胞转录组信息进行关联的现有方法仍存在多种限制。

附：英文原文

Title: ZipSeq: barcoding for real-time mapping of single cell transcriptomes

Author: Kenneth H. Hu, John P. Eichorst, Chris S. McGinnis, David M. Patterson, Eric D. Chow, Kelly Kersten, Stephen C. Jameson, Zev J. Gartner, Arjun A. Rao, Matthew F. Krummel

Issue&Volume: 2020-07-06

Abstract: Spatial transcriptomics seeks to integrate single cell transcriptomic data within the three-dimensional space of multicellular biology. Current methods to correlate a cell’s position with its transcriptome in living tissues have various limitations. We developed an approach, called ‘ZipSeq’, that uses patterned illumination and photocaged oligonucleotides to serially print barcodes (‘zipcodes’) onto live cells in intact tissues, in real time and with an on-the-fly selection of patterns. Using ZipSeq, we mapped gene expression in three settings: in vitro wound healing, live lymph node sections and a live tumor microenvironment. In all cases, we discovered new gene expression patterns associated with histological structures. In the tumor microenvironment, this demonstrated a trajectory of myeloid and T cell differentiation from the periphery inward. A combinatorial variation of ZipSeq efficiently scales in the number of regions defined, providing a pathway for complete mapping of live tissues, subsequent to real-time imaging or perturbation.

DOI: 10.1038/s41592-020-0880-2

Source: https://www.nature.com/articles/s41592-020-0880-2