纽约基因组中心Sanja Vickovic小组取得一项新突破。他们的研究开发出了结肠衰老过程中的组织和细胞时空动态。相关论文发表在2025年10月22日出版的《自然—生物技术》杂志上。
研究小组建立了横跨三个解剖区域和11个年龄组的结肠细胞和空间图谱，包括约1500个非主题肠道组织，通过空间转录组学和约40万个单核RNA测序图谱。研究团队开发了一个计算框架，cSplotch，它通过利用组织学特征在组织样本和数据模式之间共享信息，学习与年龄、组织区域和性别相关的空间分解细胞表达的分层贝叶斯模型。利用该模型，该课题组研究人员确定了沿成人结肠道和主隐窝轴的细胞和分子梯度以及与大肠衰老相关的多细胞程序。他们研究细胞和组织组织的多模态框架有助于理解细胞在组织水平病理学中的作用。
据介绍，结肠的组织结构和分子电路可以受到系统性年龄相关效应的深刻影响，但许多潜在的分子线索仍不清楚。
附：英文原文
Title: Tissue and cellular spatiotemporal dynamics in colon aging
Author: Daly, Aidan C., Cambuli, Francesco, ij, Tarmo, Ltstedt, Britta, Marjanovic, Nemanja Despot, Fernandez, Sara, Kuksenko, Olena, Smith-Erb, Matthew, Domovic, Daniel, Van Wittenberghe, Nicholas, Drokhlyansky, Eugene, Griffin, Gabriel K., Phatnani, Hemali, Bonneau, Richard, Regev, Aviv, Vickovic, Sanja
Issue&Volume: 2025-10-22
Abstract: Tissue structure and molecular circuitry in the colon can be profoundly impacted by systemic age-related effects but many of the underlying molecular cues remain unclear. Here, we build a cellular and spatial atlas of the colon across three anatomical regions and 11 age groups, encompassing ~1,500 mouse gut tissues profiled by spatial transcriptomics and ~400,000 single nucleus RNA-sequencing profiles. We develop a computational framework, cSplotch, which learns a hierarchical Bayesian model of spatially resolved cellular expression associated with age, tissue region and sex by leveraging histological features to share information across tissue samples and data modalities. Using this model, we identify cellular and molecular gradients along the adult colonic tract and across the main crypt axis and multicellular programs associated with aging in the large intestine. Our multimodal framework for the investigation of cell and tissue organization can aid in the understanding of cellular roles in tissue-level pathology.
DOI: 10.1038/s41587-025-02830-6