Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nat Methods. 2022 Nov;19(11):1490-1499. doi: 10.1038/s41592-022-01650-9. Epub 2022 Oct 24.
A central challenge in biology is obtaining high-content, high-resolution information while analyzing tissue samples at volumes relevant to disease progression. We address this here with CODA, a method to reconstruct exceptionally large (up to multicentimeter cubed) tissues at subcellular resolution using serially sectioned hematoxylin and eosin-stained tissue sections. Here we demonstrate CODA's ability to reconstruct three-dimensional (3D) distinct microanatomical structures in pancreas, skin, lung and liver tissues. CODA allows creation of readily quantifiable tissue volumes amenable to biological research. As a testbed, we assess the microanatomy of the human pancreas during tumorigenesis within the branching pancreatic ductal system, labeling ten distinct structures to examine heterogeneity and structural transformation during neoplastic progression. We show that pancreatic precancerous lesions develop into distinct 3D morphological phenotypes and that pancreatic cancer tends to spread far from the bulk tumor along collagen fibers that are highly aligned to the 3D curves of ductal, lobular, vascular and neural structures. Thus, CODA establishes a means to transform broadly the structural study of human diseases through exploration of exhaustively labeled 3D microarchitecture.
生物学的一个核心挑战是在分析与疾病进展相关的组织样本时，获取高含量、高分辨率的信息。我们在这里使用 CODA 解决了这个问题，这是一种使用连续切片的苏木精和伊红染色组织切片以亚细胞分辨率重建异常大（高达立方厘米级）组织的方法。在这里，我们展示了 CODA 重建胰腺、皮肤、肺和肝脏组织中三维（3D）不同微观解剖结构的能力。CODA 允许创建易于量化的组织体积，适用于生物学研究。作为一个测试平台，我们评估了分支胰腺导管系统中肿瘤发生过程中人类胰腺的微观解剖结构，标记了十个不同的结构，以检查在肿瘤进展过程中的异质性和结构转化。我们表明，胰腺癌前病变发展成独特的 3D 形态表型，并且胰腺癌往往沿着与导管、小叶、血管和神经结构的 3D 曲线高度对齐的胶原纤维远离肿瘤主体扩散。因此，CODA 通过探索详尽标记的 3D 微观结构，为广泛探索人类疾病的结构研究提供了一种手段。
