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Area of Science:

  • Gastroenterology and Aging Research
  • Computational Biology and Spatial Omics

Background:

  • Systemic aging significantly impacts colon tissue structure and molecular function.
  • The specific molecular signals driving age-related colonic changes are not fully understood.

Purpose of the Study:

  • To create a comprehensive cellular and spatial atlas of the mouse colon across aging.
  • To identify molecular and cellular gradients and aging-associated multicellular programs within the colon.

Main Methods:

  • Profiling of approximately 1,500 mouse gut tissues using spatial transcriptomics.
  • Analysis of around 400,000 single nucleus RNA-sequencing profiles.
  • Development and application of a novel computational framework, cSplotch, for integrated analysis.

Main Results:

  • Identification of distinct cellular and molecular gradients along the colonic tract and crypt axis.
  • Discovery of multicellular programs associated with aging in the large intestine.
  • Leveraging histological features to enhance information sharing across samples and data types.

Conclusions:

  • The developed multi-modal framework provides insights into cell and tissue organization during aging.
  • This atlas aids in understanding the role of cellular dynamics in age-related colonic pathology.