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<p>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.</p>

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Tissue and cellular spatiotemporal dynamics in colon aging

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月22日

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  • Aidan C. Daly,
  • Francesco Cambuli,
  • Tarmo Äijö,
  • Britta Lötstedt,
  • Nemanja Despot Marjanovic,
  • Sara Fernandez,
  • Olena Kuksenko,
  • Matthew Smith-Erb,
  • Daniel Domovic,
  • Nicholas Van Wittenberghe,
  • Eugene Drokhlyansky,
  • Gabriel K. Griffin,
  • Hemali Phatnani,
  • Richard Bonneau,
  • Aviv Regev,
  • Sanja Vickovic

摘要

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.