Microscopic examination of spatial transcriptome using Seq-Scope.

Microscopic examination of spatial transcriptome using Seq-Scope.
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使用Seq-Scope的空间转录组的显微镜检查。

DOI:
10.1016/j.cell.2021.05.010
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发表时间:
2021-06-24
期刊:
影响因子:
64.5
通讯作者:
Lee JH
Lee JH
中科院分区:
生物学1区
文献类型:
--
作者:
Cho CS;Xi J;Si Y;Park SR;Hsu JE;Kim M;Jun G;Kang HM;Lee JH

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空间条码技术有可能揭示转录图谱的组织细节;然而,目前它们受到低分辨率的限制。在这里,我们报告了Seq-Scope,这是一种分辨率与光学显微镜相当的空间条形码技术。SEQ-SCOPE基于使用Illumina测序平台对随机条形码的单分子寡核苷酸进行固相扩增。得到的用空间坐标标注的簇被处理以揭示RNA捕获的部分。这些捕获RNA的条形码簇定义了彼此相距约0.5-0.8μm的序列范围的像素。从组织切片上,Seq-Scope显示了多个组织尺度上的空间转录组异质性,包括根据门静脉-中央(肝脏)、隐窝表面(结肠)和炎症-纤维化(受损的肝脏)轴的组织分区,包括单细胞类型和亚型的细胞成分,以及细胞核和细胞质的亚细胞结构。SEQ-SCOPE是快速、直接、精确和易于实现的,并使空间单细胞分析可供广泛的生物医学研究人员使用。SEQ-SCOPE使用空间条形码和Illumina测序平台实现亚微米分辨率的空间转录,使各种组织在细胞和亚细胞水平上的转录异质性得以可视化。
Spatial barcoding technologies have the potential to reveal histological details of transcriptomic profiles; however, they are currently limited by their low resolution. Here we report Seq-Scope, a spatial barcoding technology with a resolution comparable to an optical microscope. Seq-Scope is based on a solid-phase amplification of randomly barcoded single-molecule oligonucleotides using an Illumina sequencing platform. The resulting clusters annotated with spatial coordinates are processed to expose RNA-capture moiety. These RNA-capturing barcoded clusters define the pixels of Seq-Scope that are approximately 0.5-0.8 μm apart from each other. From tissue sections, Seq-Scope visualizes spatial transcriptome heterogeneity at multiple histological scales, including tissue zonation according to the portal-central (liver), crypt-surface (colon) and inflammation-fibrosis (injured liver) axes, cellular components including single cell types and subtypes, and subcellular architectures of nucleus and cytoplasm. Seq-scope is quick, straightforward, precise and easy-to-implement, and makes spatial single cell analysis accessible to a wide group of biomedical researchers. Seq-Scope uses spatial barcoding and the Illumina sequencing platform to achieve sub-micron resolution spatial transcriptomics, enabling the visualization of transcriptomic heterogeneity at the cellular and subcellular level in various tissues.
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