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Tissue and cellular spatiotemporal dynamics in colon aging.

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This study maps colon tissue cells and their spatial organization across ages, revealing molecular changes linked to aging in the large intestine. This work aids understanding of cellular roles in colonic tissue pathology.

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Area of Science:

  • Gastroenterology
  • Computational Biology
  • Aging Research

Background:

  • Systemic aging profoundly impacts colon tissue structure and molecular circuitry.
  • Underlying molecular cues driving age-related colonic changes remain largely unclear.

Purpose of the Study:

  • To create a comprehensive cellular and spatial atlas of the colon across different ages and anatomical regions.
  • To identify molecular gradients and multicellular programs associated with aging in the large intestine.

Main Methods:

  • Profiling ~1,500 mouse gut tissues using spatial transcriptomics and ~400,000 single nucleus RNA-sequencing profiles.
  • Developing a computational framework, cSplotch, for a hierarchical Bayesian model of spatially resolved cellular expression.
  • Leveraging histological features to integrate information across tissue samples and data modalities.

Main Results:

  • Identification of cellular and molecular gradients along the adult colonic tract and crypt axis.
  • Discovery of multicellular programs associated with aging in the large intestine.
  • Establishment of a multimodal framework for investigating cell and tissue organization.

Conclusions:

  • The developed atlas and computational framework provide insights into age-related changes in the colon.
  • This research aids in understanding the cellular roles within tissue-level pathology of the large intestine.
  • The study advances the investigation of cell and tissue organization in aging.