芝加哥大学Joshua A. Weinstein研究组在研究中取得进展。他们报道了空间转录组成像的一个完整的有机体使用体积DNA显微镜。2025年3月27日出版的《自然—生物技术》发表了这项成果。

在这里，该课题组人员开发了一种能够在一次测量中对转录组、基因型和形态进行体积成像的技术，而不依赖于空间组织或基因序列的先验知识。他们的方法将DNA显微镜扩展到涉及107个分子的三维尺度，通过形成一个分布的分子间网络，该网络由近端独特的DNA条形码标记标本内的互补DNA分子。在对DNA编码网络进行测序后，通过测地线光谱嵌入推断出分子位置的图像，这是一种降维方法，该课题组人员认为它特别适合于这种数据逆问题。应用全转录组体积DNA显微镜对完整的斑马鱼胚胎，研究组证明了三维图像推断概括了斑马鱼的形态和已知的基因表达模式，捕获了基因序列的空间组织。他们将空间遗传测量扩展到三维，独立于先前的模板，为生物组织中基因组学和形态学的详细联合分辨率打开了大门。

据了解，淋巴组织、神经组织和肿瘤组织在遗传上独特的微环境中表现出三维相互作用的复杂生理机能。

附：英文原文

Title: Spatial transcriptomic imaging of an intact organism using volumetric DNA microscopy

Author: Qian, Nianchao, Weinstein, Joshua A.

Issue&Volume: 2025-03-27

Abstract: Lymphatic, nervous and tumor tissues exhibit complex physiology arising from three-dimensional interactions within genetically unique microenvironments. Here we develop a technology capable of volumetrically imaging transcriptomes, genotypes and morphologies in a single measurement, without relying on prior knowledge of spatial organization or genetic sequences. Our method extends DNA microscopy into three dimensions at scales involving 107 molecules by forming a distributed intermolecular network of proximal unique DNA barcodes tagging complementary DNA molecules inside the specimen. After sequencing the DNA-encoded network, an image of molecular positions is inferred using geodesic spectral embeddings, a dimensionality reduction approach that we show to be especially suitable for this data-inverse problem. Applying whole-transcriptome volumetric DNA microscopy to intact zebrafish embryos, we demonstrate that three-dimensional image inference recapitulates zebrafish morphology and known gene expression patterns, capturing the spatial organization of gene sequences. Our extension of spatial genetic measurements to three dimensions, independent of prior templates, opens the door to detailed joint resolution of genomics and morphology in biological tissues.

DOI: 10.1038/s41587-025-02613-z

Source: https://www.nature.com/articles/s41587-025-02613-z