美国约翰霍普金斯大学Pei-Hsun Wu和Denis Wirtz研究组合作开发出了CODA，即细胞分辨率下的大组织定量三维(3D)重建。这一研究成果于2022年10月24日发表在国际顶尖学术期刊《自然—方法学》上。

他们用CODA来解决分辨率低的问题，这是一种用苏木精和伊红染色的连续组织切片，以亚细胞分辨率重建超大(高达立方厘米)组织的方法。他们展示了CODA在胰腺、皮肤、肺和肝脏组织中重建3D独特显微解剖结构的能力。CODA允许创建易于量化的组织，适合生物研究。作为一个实验平台，他们评估了分支胰管系统肿瘤发生过程中人类胰腺的微观解剖，标记了10个不同的结构，以检验肿瘤进展过程中的异质性和结构转化。

他们发现，胰腺癌前病变发展为独特的三维形态表型，胰腺癌倾向于沿胶原纤维扩散，远离大块肿瘤，胶原纤维与导管、小叶、血管和神经结构的三维曲线高度一致。因此，CODA建立了一种通过探索充分标记的3D微结构，广泛地改变人类疾病的结构研究的手段。

据了解，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的同时，获得高含量、高分辨率的信息。

附：英文原文

Title: CODA: quantitative 3D reconstruction of large tissues at cellular resolution

Author: Kiemen, Ashley L., Braxton, Alicia M., Grahn, Mia P., Han, Kyu Sang, Babu, Jaanvi Mahesh, Reichel, Rebecca, Jiang, Ann C., Kim, Bridgette, Hsu, Jocelyn, Amoa, Falone, Reddy, Sashank, Hong, Seung-Mo, Cornish, Toby C., Thompson, Elizabeth D., Huang, Peng, Wood, Laura D., Hruban, Ralph H., Wirtz, Denis, Wu, Pei-Hsun

Issue&Volume: 2022-10-24

Abstract: 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.

DOI: 10.1038/s41592-022-01650-9

Source: https://www.nature.com/articles/s41592-022-01650-9