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Spatiotemporal Transcriptomic Atlas of Mouse Organogenesis Using DNA Nanoball Patterned Arrays

Cell(2022)

BGI Shenzhen | Whitehead Inst Biomed Res | Chinese Acad Sci | Pompeu Fabra Univ UPF | Univ Cambridge | Guangzhou Lab | Guangdong Acad Med Sci | Univ Copenhagen | Univ Oxford | KTH Royal Inst Technol

Cited 609|Views138
Abstract
Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.
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Key words
spatial transcriptomics,single-cell,cell atlas,mouse organogenesis,development,cell lineages,progenitors,cell differentiation,brain,developmental diseases
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要点】:本文通过结合DNA纳米球阵列和组织RNA捕获技术开发了一种新型时空转录组测序方法Stereo-seq,实现了对大型组织切片的高分辨率和灵敏度转录组分析,为研究哺乳动物器官发生中的细胞命运决定和分子基础提供了系统化应用的新工具。

方法】:采用DNA纳米球(DNB)模式化阵列与组织RNA捕获相结合的技术。

实验】:研究了小鼠器官发生过程中转录变化的动态和方向性,并将发育疾病相关基因的表达映射到全局转录组图上,以确定组织的时空易感窗口。使用的数据集为Stereo-seq产生的器官发生时空转录组数据集,结果显示了大脑发育过程中不同区域的基因表达模式和神经元迁移分化情况,以及发育疾病相关基因的时空表达模式。