近日，德国柏林夏里特医学院Nikolaus Rajewsky等研究人员合作开发出3D高分辨空间转录组学。相关论文于2024年6月24日在线发表在《细胞》杂志上。
研究人员报告了Open-ST，这是一种基于测序的开源实验和计算资源，用于应对这些挑战并研究2D和3D组织的分子组织。在小鼠大脑中，Open-ST捕获了亚细胞分辨率的转录本，并重建了细胞类型。在原发性头颈部肿瘤和患者匹配的健康/转移淋巴结中，Open-ST捕获了免疫、基质和肿瘤群体在空间上的多样性，并通过基于成像的空间转录组学（ST）进行了验证。不同的细胞状态围绕着肿瘤中的细胞-细胞交流热点（而非转移灶）。
令人震惊的是，转移淋巴结的3D重建和多模态分析揭示了2D中不可见的空间连续结构，以及3D肿瘤/淋巴结边界的潜在生物标记物。所有实验方案和软件均可在https://rajewsky-lab.github.io/openst上获取。
据介绍，ST方法揭示了组织发育、稳态或疾病的分子机制。然而，人们需要易于使用、高分辨率、低成本和3D可扩展的方法。
附：英文原文
Title: Open-ST: High-resolution spatial transcriptomics in 3D
Author: Marie Schott, Daniel León-Perián, Elena Splendiani, Leon Strenger, Jan Robin Licha, Tancredi Massimo Pentimalli, Simon Schallenberg, Jonathan Alles, Sarah Samut Tagliaferro, Anastasiya Boltengagen, Sebastian Ehrig, Stefano Abbiati, Steffen Dommerich, Massimiliano Pagani, Elisabetta Ferretti, Giuseppe Macino, Nikos Karaiskos, Nikolaus Rajewsky
Issue&Volume: 2024-06-24
Abstract: Spatial transcriptomics (ST) methods unlock molecular mechanisms underlying tissuedevelopment, homeostasis, or disease. However, there is a need for easy-to-use, high-resolution,cost-efficient, and 3D-scalable methods. Here, we report Open-ST, a sequencing-based,open-source experimental and computational resource to address these challenges andto study the molecular organization of tissues in 2D and 3D. In mouse brain, Open-STcaptured transcripts at subcellular resolution and reconstructed cell types. In primaryhead-and-neck tumors and patient-matched healthy/metastatic lymph nodes, Open-ST capturedthe diversity of immune, stromal, and tumor populations in space, validated by imaging-basedST. Distinct cell states were organized around cell-cell communication hotspots inthe tumor but not the metastasis. Strikingly, the 3D reconstruction and multimodalanalysis of the metastatic lymph node revealed spatially contiguous structures notvisible in 2D and potential biomarkers precisely at the 3D tumor/lymph node boundary.All protocols and software are available at https://rajewsky-lab.github.io/openst.
DOI: 10.1016/j.cell.2024.05.055
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00636-6