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定制微流控芯片设计实现了具有宽视场的经济高效的三维时空转录组学。

Custom microfluidic chip design enables cost-effective three-dimensional spatiotemporal transcriptomics with a wide field of view.

机构信息

Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.

出版信息

Nat Genet. 2024 Oct;56(10):2259-2270. doi: 10.1038/s41588-024-01906-4. Epub 2024 Sep 10.

DOI:10.1038/s41588-024-01906-4
PMID:39256584
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11525186/
Abstract

Spatial transcriptomic techniques offer unprecedented insights into the molecular organization of complex tissues. However, integrating cost-effectiveness, high throughput, a wide field of view and compatibility with three-dimensional (3D) volumes has been challenging. Here we introduce microfluidics-assisted grid chips for spatial transcriptome sequencing (MAGIC-seq), a new method that combines carbodiimide chemistry, spatial combinatorial indexing and innovative microfluidics design. This technique allows sensitive and reproducible profiling of diverse tissue types, achieving an eightfold increase in throughput, minimal cost and reduced batch effects. MAGIC-seq breaks conventional microfluidics limits by enhancing barcoding efficiency and enables analysis of whole postnatal mouse sections, providing comprehensive cellular structure elucidation at near single-cell resolution, uncovering transcriptional variations and dynamic trajectories of mouse organogenesis. Our 3D transcriptomic atlas of the developing mouse brain, consisting of 93 sections, reveals the molecular and cellular landscape, serving as a valuable resource for neuroscience and developmental biology. Overall, MAGIC-seq is a high-throughput, cost-effective, large field of view and versatile method for spatial transcriptomic studies.

摘要

空间转录组技术为复杂组织的分子结构提供了前所未有的见解。然而，将成本效益、高通量、宽视场和与三维（3D）体积的兼容性结合起来一直具有挑战性。在这里，我们介绍了用于空间转录组测序的微流控辅助网格芯片（MAGIC-seq），这是一种将碳二亚胺化学、空间组合索引和创新的微流控设计相结合的新方法。该技术可以敏感且可重复地分析多种组织类型，实现了 8 倍的通量增加、最小的成本和减少的批次效应。MAGIC-seq 通过提高条形码效率打破了传统微流控的限制，并能够分析整个新生小鼠切片，提供接近单细胞分辨率的全面细胞结构阐明，揭示转录变化和小鼠器官发生的动态轨迹。我们由 93 个切片组成的发育中老鼠大脑的 3D 转录组图谱揭示了分子和细胞景观，为神经科学和发育生物学提供了有价值的资源。总体而言，MAGIC-seq 是一种高通量、经济高效、大视场和多功能的空间转录组学研究方法。

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