Department of Gene Technology, KTH Royal Institute of Technology, SciLifeLab, Stockholm, Sweden.
Systems Genomics Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Nat Commun. 2023 Oct 14;14(1):6500. doi: 10.1038/s41467-023-42237-y.
Several important human infectious diseases are caused by microscale-sized parasitic nematodes like filarial worms. Filarial worms have their own spatial tissue organization; to uncover this tissue structure, we need methods that can spatially resolve these miniature specimens. Most filarial worms evolved a mutualistic association with endosymbiotic bacteria Wolbachia. However, the mechanisms underlying the dependency of filarial worms on the fitness of these bacteria remain unknown. As Wolbachia is essential for the development, reproduction, and survival of filarial worms, we spatially explored how Wolbachia interacts with the worm's reproductive system by performing a spatial characterization using Spatial Transcriptomics (ST) across a posterior region containing reproductive tissue and developing embryos of adult female Brugia malayi worms. We provide a proof-of-concept for miniature-ST to explore spatial gene expression patterns in small sample types, demonstrating the method's ability to uncover nuanced tissue region expression patterns, observe the spatial localization of key B. malayi - Wolbachia pathway genes, and co-localize the B. malayi spatial transcriptome in Wolbachia tissue regions, also under antibiotic treatment. We envision our approach will open up new avenues for the study of infectious diseases caused by micro-scale parasitic worms.
几种重要的人类传染病是由微尺度大小的寄生线虫引起的，例如丝虫。丝虫具有自己的空间组织；为了揭示这种组织结构，我们需要能够空间解析这些微型标本的方法。大多数丝虫与内共生细菌沃尔巴克氏体（Wolbachia）形成了共生关系。然而，丝虫对这些细菌的适应性依赖的机制尚不清楚。由于沃尔巴克氏体对丝虫的发育、繁殖和生存是必不可少的，我们通过在包含生殖组织和成年雌性布鲁氏虫（Brugia malayi）发育胚胎的后区进行空间转录组学（Spatial Transcriptomics，ST）空间特征分析，来探索沃尔巴克氏体与丝虫生殖系统的相互作用。我们提供了一个微小 ST 的概念验证，以探索小样本类型中的空间基因表达模式，展示了该方法揭示细微组织区域表达模式的能力，观察关键的 B. malayi-Wolbachia 途径基因的空间定位，并在抗生素处理下，将 B. malayi 的空间转录组共定位在沃尔巴克氏体组织区域。我们设想我们的方法将为研究由微尺度寄生线虫引起的传染病开辟新途径。
