Slide-tags: scalable, single-nucleus barcoding for multi-modal spatial genomics

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 constructed. Missing from these measurements, however, 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 input into a wide variety of single-nucleus profiling assays. We used Slide-tags to profile two different stages of development in the mouse brain. Slide-tags was used to spatially barcode nuclei from 20-micron thick fresh frozen tissue sections. These spatially barcoded nuclei were then used as input for 10x Genomics Chromium v3.1 snRNA-seq.近年来的技术革新已实现单个细胞内基因表达与表观遗传调控的高通量定量分析，彻底改变了我们对复杂组织构建机制的认知。然而，这类检测手段仍存在一项短板：无法常规且便捷地对已完成谱分析的细胞进行空间定位。为此我们开发了Slide-tags（滑动标签）技术：将携带已知位置标识的DNA条形码微珠制备的空间条形码寡核苷酸，对完整组织切片内的单个细胞核进行标记。经此标记的细胞核可作为输入样本，用于多种单细胞核谱分析实验。我们利用Slide-tags技术对小鼠大脑发育的两个不同阶段开展了谱分析实验：针对厚度为20微米的新鲜冷冻组织切片中的细胞核完成空间条形码标记，随后将此类带有空间条形码的细胞核作为输入样本，用于10x Genomics Chromium v3.1单细胞核RNA测序（snRNA-seq）。