# Core C: Biological Analysis Core

> **NIH NIH U54** · YALE UNIVERSITY · 2021 · $506,635

## Abstract

PROJECT SUMMARY – Core C (Biological Analysis Core)
Cellular senescence in human primary lymphoid organs such as bone marrow (BM) and thymus, and
secondary lymphoid organs such as tonsil and lymph nodes (LNs) have been reported to show complex roles
in normal hematopoiesis, immune function, aging, and disease development. These organs are among the
most active, dynamic, and plastic physiologic systems. How cellular senescence is associated with stress-
induced or age-related functional impairment, what types or subtypes of senescent cells are present and their
spatial heterogeneity in the lymphoid tissues and how these cells impact the tissue environments remain poorly
understood, precluding the development of strategies to target these cells to improve healthspan/lifespan or
harnessing these cells or secreted factors to promote tissue remodeling and repair. Yale TMC Core C:
Biological Analysis Core (BAC) will deploy a suite of high-resolution, high-content and high-throughput single-
cell & spatial omics technologies to construct comprehensive maps of cellular senescence and the associated
environments in primary human cells and human lymphoid tissues. Four major biological analyses will be
performed: single-cell high-plex protein secretome profiling, single-cell proteo-transcriptomic sequencing
(scCITE-seq), spatial proteo-transcriptomic sequencing at cellular level (DBiT-seq), and spatial molecular
imaging (SMI) at single molecule resolution. Specifically, we will conduct (1) single-cell protein secretome
profiling of SAPS heterogeneity using induced senescent cell models and body fluids, (2) single-cell and spatial
proteo-transcriptomic sequencing to map senescent cells and environments in human lymphoid tissues. (3)
high-plex proteo-transcriptomic spatial molecular imaging of lymphoid tissues. We envision that the proposed
project will generate extensive multiscale, multimodality, and multifaceted data to characterize phenotypic,
functional and spatial heterogeneity of senescent cells in response to multiple inducers or modifiers, identify
biomarkers of senescent cell subtypes and neighborhoods, and construct maps and atlases of cellular
senescence and environments in primary and secondary lymphoid organs of humans over longitudinal time
frames, representing a highly valuable resource for a wide range of biomedical research.

## Key facts

- **NIH application ID:** 10384403
- **Project number:** 1U54AG076043-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Rong Fan
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $506,635
- **Award type:** 1
- **Project period:** 2021-09-30 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10384403

## Citation

> US National Institutes of Health, RePORTER application 10384403, Core C: Biological Analysis Core (1U54AG076043-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10384403. Licensed CC0.

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