Tissue and cellular spatiotemporal dynamics in colon aging
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.
Authors
- Nemanja D. Marjanovic
- Aviv Regev (ORCID: https://orcid.org/0000-0003-3293-3158)
- Tarmo Äijö (ORCID: https://orcid.org/0000-0002-3008-4634)
- Eugene Drokhlyansky (ORCID: https://orcid.org/0000-0002-1939-3559)
- Olena Kuksenko (ORCID: https://orcid.org/0000-0002-1728-4957)
- Sara Fernández‐García (ORCID: https://orcid.org/0000-0003-2281-4526)
- Nicholas Van Wittenberghe (ORCID: https://orcid.org/0000-0002-7653-9729)
- Britta Lötstedt
- Hemali Phatnani (ORCID: https://orcid.org/0000-0002-6571-3891)
- Richard Bonneau (ORCID: https://orcid.org/0000-0003-4354-7906)
- Daniel Domović (ORCID: https://orcid.org/0000-0003-4576-7988)
- Sanja Vicković (ORCID: https://orcid.org/0000-0003-0985-9885)
- Francesco Cambuli
- Matthew Smith-Erb
- Aidan C. Daly (ORCID: https://orcid.org/0000-0003-4447-8623)
- Gabriel K. Griffin (ORCID: https://orcid.org/0000-0002-4042-6757)
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Columbia University Irving Medical Center (US)
- Skin Cancer Foundation (US)
- Science for Life Laboratory (SE)
- HES-SO Genève (CH)
- Gender Studies (CZ)
- Gene Therapy Laboratory (FR)
- Human Technopole (IT)
- New York Genome Center (US)
- Flatiron Health (United States) (US)
- Flatiron Institute (US)
- Massachusetts Institute of Technology (US)
- KTH Royal Institute of Technology (SE)
Publication Details
- Journal
- Nature Biotechnology
- Published
- 2025-10-22
- DOI
- https://doi.org/10.1038/s41587-025-02830-6
- Citations
- 3
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 2.42