近日，美国哈佛大学Fei Chen等研究人员合作发现，Slide-tags可为多模式空间基因组学提供单核条形码。2023年12月13日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员开发了一种名为“Slide-tags”的策略，在完整的组织切片上用空间条形码寡核苷酸标记单个细胞核，这些寡核苷酸来自已知位置的DNA条形珠。然后，这些被标记的细胞核可作为各种单个细胞核分析测试的输入。将Slide-tags应用于小鼠海马，其以低于10μm的空间分辨率定位细胞核，并提供与普通单核RNA序列数据质量无异的全转录组数据。为了证明Slide-tags可以应用于多种人体组织，人们对大脑、扁桃体和黑色素瘤进行了检测。

研究人员揭示了大脑皮层中细胞类型特异性的空间变化基因表达，以及驱动淋巴组织中B细胞成熟的空间背景受体配体相互作用。Slide-tags的一个主要优点是它很容易适应几乎所有单细胞测量技术。作为原理验证，研究人员对来自转移性黑色素瘤的相同细胞中的开放染色质、RNA和T细胞受体（TCR）序列进行了多组学测量，并确定了在空间不同的微环境中驱动癌细胞状态转变的转录因子基团。Slide-tags提供了一个通用平台，可将已建立的单细胞测量汇编导入空间基因组学库。

据了解，最近的技术创新实现了对单个细胞内基因表达和表观遗传调控的高通量量化，改变了人们对复杂组织如何构建的理解。然而，在这些测量中缺少的是对这些剖面细胞进行常规、简便的空间定位的能力。

附：英文原文

Title: Slide-tags enables single-nucleus barcoding for multimodal spatial genomics

Author: Russell, Andrew J. C., Weir, Jackson A., Nadaf, Naeem M., Shabet, Matthew, Kumar, Vipin, Kambhampati, Sandeep, Raichur, Ruth, Marrero, Giovanni J., Liu, Sophia, Balderrama, Karol S., Vanderburg, Charles R., Shanmugam, Vignesh, Tian, Luyi, Iorgulescu, J. Bryan, Yoon, Charles H., Wu, Catherine J., Macosko, Evan Z., Chen, Fei

Issue&Volume: 2023-12-13

Abstract: Recent technological innovations have enabled the high-throughput quantification of gene expression and epigenetic regulation within individual cells, transforming our understanding of how complex tissues are constructed1,2,3,4,5,6. However, missing from these measurements is the ability to routinely and easily spatially localize these profiled cells. We developed a strategy, Slide-tags, in which single nuclei within an intact tissue section are tagged with spatial barcode oligonucleotides derived from DNA-barcoded beads with known positions. These tagged nuclei can then be used as an input into a wide variety of single-nucleus profiling assays. Application of Slide-tags to the mouse hippocampus positioned nuclei at less than 10μm spatial resolution and delivered whole-transcriptome data that are indistinguishable in quality from ordinary single-nucleus RNA-sequencing data. To demonstrate that Slide-tags can be applied to a wide variety of human tissues, we performed the assay on brain, tonsil and melanoma. We revealed cell-type-specific spatially varying gene expression across cortical layers and spatially contextualized receptor–ligand interactions driving B cell maturation in lymphoid tissue. A major benefit of Slide-tags is that it is easily adaptable to almost any single-cell measurement technology. As a proof of principle, we performed multiomic measurements of open chromatin, RNA and T cell receptor (TCR) sequences in the same cells from metastatic melanoma, identifying transcription factor motifs driving cancer cell state transitions in spatially distinct microenvironments. Slide-tags offers a universal platform for importing the compendium of established single-cell measurements into the spatial genomics repertoire.

DOI: 10.1038/s41586-023-06837-4

Source: https://www.nature.com/articles/s41586-023-06837-4