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Fluorescence-Guided Spatial Mapping of p21-Expressing Senescent Cells in Aged Liver at Single-Cell Resolution.
Jer-En Hsu1, Binsheng Wang2,3, Yongha Hwang1,4
1Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Biomolecules
|May 4, 2026
Summary
Scientists mapped senescent cells in aging livers using a novel spatial transcriptomic method. This approach identified diverse cell types exhibiting senescence, revealing distinct aging-associated stress programs for better understanding aging mechanisms.
Area of Science:
- Cellular senescence
- Aging research
- Spatial transcriptomics
Background:
- Aging is characterized by senescent cells, which contribute to age-related diseases but are difficult to study due to scarcity and heterogeneity.
- Senescent cells, while non-dividing, remain viable and impact tissue function and disease pathogenesis.
- Understanding senescent cell heterogeneity and function is crucial for developing targeted aging interventions.
Purpose of the Study:
- To develop and apply a high-resolution spatial transcriptomic approach for precise mapping and profiling of senescent cells in vivo.
- To identify diverse senescent cell types and their associated molecular programs within aged liver tissue.
- To investigate distinct aging-associated cellular stress programs beyond p21 expression.
Main Methods:
- Development of a fluorescence-guided spatial transcriptomic profiling technique.
- In situ analysis of p21-reporter-positive cells in aged liver tissue.
- Transcriptomic and spatial positioning analysis of senescent and interferon-stimulated gene-expressing cells.
Main Results:
- Unbiased detection and identification of a senescent cell population with diverse identities (hepatocytes, macrophages, neutrophils, plasma cells).
- Activated macrophages and hepatic stellate cells showed higher p21 positivity.
- Heterogeneous senescence-associated secretory phenotype (SASP) programs with distinct inflammatory and remodeling signatures were observed across cell types and locations.
- Identification of a distinct aging-associated stress program marked by interferon-stimulated gene expression, with limited overlap with senescent cells.
Conclusions:
- The developed spatial transcriptomic framework enables high-resolution, single-cell mapping of senescence in situ.
- This method delineates both senescent cell type specificity and cell-identity-independent senescence programs.
- The findings advance the comprehensive understanding of regulatory mechanisms underlying aging and senescence.
