Resources: Posters

Identifying subsets of Senescent Cells using a Platform that Converges Key Hallmarks of Senescence to the Same Single Cells

October 20, 2025

Biomarkers of Aging

Annarita Scaramozza, Ph.D., Staff Scientist

Keywords: R3200 Platform, CellCage™ technology, Cellular senescence, Aging biomarkers, Senescence hallmarks, Multi-modal single-cell analysis, Metabolic disease

Keywords: R3200 Platform, CellCage™ technology, Cellular senescence, Aging biomarkers, Senescence hallmarks, Multi-modal single-cell analysis, Metabolic disease

Presented by:
Annarita Scaramozza, Ph.D., Staff Scientist
Presented at:
November 7, 2025

This study demonstrates a powerful approach to identifying distinct subsets of senescent cells by converging multiple hallmarks of senescence—such as morphology, secretory activity, and gene expression—to the same individual cells. Utilizing the R3200 Platform and CellCage™ technology, the research overcomes the limitations of single-marker identification, providing a high-resolution, multimodal map of cellular aging. The results establish a new standard for characterizing senescent heterogeneity in aging and metabolic disease research.

Case Study: Functional Profiling of Microglia in Neuroinflammation

Link microglial behavior to gene expression at single-cell resolution, for insight into neuroinflammation, drug response, and immune dysfunction in CNS disease.

View Case Study Details

Researchers used the Cellanome R3200 to enclose individual microglia with fluorescent particles and track phagocytosis over 12 hours via fluorescent imaging. Each cell’s transcriptome was then sequenced, linking activity levels to gene expression.  

What they found: 

High-activity microglia upregulated genes in complement signaling, lipid metabolism, and lysosomal function–key pathways in neuroinflammation and repair. 

Why it matters: 

This approach overcomes key limitations in standard assays by capturing phagocytic function and gene expression in the same individual cells without dissociation, pooling, or inference. It enables a direct, scalable readout of immune heterogeneity, and reveals the transcriptional programs driving effective or impaired microglial responses.  

What’s next: 

Extend to co-cultures by layering enclosed microglia over intact neuronal networks. Study how cell-cell interactions shape phagocytic behavior and fate. Combine with cytokines, CRISPR libraries, or immunotherapies to generate time-resolved, multi-modal datasets that can be used for MoA analysis, early biomarker discovery, and AI-guided modeling in CNS disease. 

Case Study: Modeling Synapse Formation and Developmental Trajectories in 3D

Track development, function, and gene expression in intact neurospheres, a human-relevant 3D model increasingly vital as regulators move away from animal studies.

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Stem-cell-derived neurospheres offer a robust 3D model of early brain development, but standard assays disrupt their structure and miss critical dynamics.  

Approach:

Using the Cellanome R3200, the research team explored,

  • Hundreds of intact neurospheres (100–200 cells each) were cultured inside individual CellCage™ enclosures. 
  • Axon extension, synapse formation and calcium activity were tracked over multiple days. 
  • End-point RNA-Seq was linked back to each neurosphere’s functional behavior. 
  • UMAP clustering revealed lineage-specific gene programs, validated by fluorescent markers.  
What's next:

This lays the groundwork for CRISPR-based multimodal screens to probe mechanisms of development, degeneration, and repair within preserved 3D architecture. 

Why it matters:

As the FDA and others move to reduce reliance on animal models, human-relevant in vitro systems like this are increasingly essential. 

FAQ's

How does the R3200 Platform help identify subsets of senescent cells?

The R3200 Platform enables the longitudinal tracking of individual cells, allowing researchers to observe multiple senescence hallmarks simultaneously. By linking real-time functional data with end-point transcriptomics through CellCage™ technology, the platform can distinguish between various senescent phenotypes that appear identical under traditional single-marker assays.

Why is it important to converge "hallmarks of senescence" to the same single cells?

Senescence is a complex, multi-stage process with no single universal marker. Converging hallmarks like morphology, lysosomal activity, and RNA expression to the same cell ensures that identifying a "senescent" state is biologically accurate and allows for the discovery of rare or highly specific cellular subsets involved in aging.

How does CellCage™ technology improve the study of cellular senescence?

CellCage™ technology secures cells in a stable microenvironment, preventing the loss of delicate senescent phenotypes during the analysis process. This non-destructive approach allows for the continuous monitoring of the Senescence-Associated Secretory Phenotype (SASP) and other dynamic behaviors before moving to high-resolution sequencing.