# Molecular Regulation of Stem Cell Aging

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $273,757

## Abstract

SUMMARY
 The Single Cell and Spatial Proteomics Core will provide access to highly multiplexed single
cell proteomic assays to reveal aging-related regulatory cell-states and their phenotypic identification and
localization. Based on innovative technologies pioneered in our lab, single cell mass cytometry (i.e.
CyTOF, for cell suspensions)1-2 and Multiplexed Ion Beam Imaging (i.e. MIBI, for nanometer-scale spatial
tissue imaging)3-5, the Core will provide deep cell state characterization of cell preparations and tissues
derived from the research projects during this grant cycle. Using elemental mass isotopes as reporters,
these technologies facilitate robust, inexpensive, single cell analyses quantifying 50+ features
simultaneously on millions of cells per experiment. We have had extensive experience applying these
technologies to derive deep phenotypic profiles of immune and intrinsic cells from numerous tissues,
including the hematopoietic1-2,6-9, central nervous system5,10-12, and muscle13-14. Besides cells
composition of these systems, we have routinely created and applied single cell assays to capture
functional and regulatory cell states, including: signaling1-2,6,8,15-17, cell cycle18-19, metabolism20, and
regulatory chromatin content4-5,14,21-22. All these established assays will be available to the research
projects and performed by the Core.
 The Single Cell and Spatial Proteomics Core will work with each project to create (spatial)
progenitor cell tissue atlases that captures deep cellular phenotypes and function with age,
focusing on single cell metabolic status and chromatin content. Overall, the products of these new
and integrated single cell assays will support the aims of Projects 1-3 for this funding cycle. These
include: integration of single cell metabolic and chromatin states with spatial localization in muscle
progenitor cells as they age (Project 1, Rando); spatial profiling of neural stem cell phenotypes with
metabolic use and chromatin modifications (Project 2, Brunet); tracking the phenotype and augmented
metabolism in aging and expanding hematopoietic progenitor cells along with the identity and localization
of their myeloid derivatives (Project 3 – Goodell).
 With novel single cell assay technologies, we have also established extensive computational
methods for single-cell analysis, including the first uses of principle component analysis (PCA)1,
stochastic neighborhood embedding (tSNE)23, spanning tree analysis of density normalized events
(SPADE, clustering/graphing)1,24, pseudo-time ordering (i.e. `cell clocks', Wanderlust)2, and spatial
enrichment approximation in imaging on highly multiplexed single cell data4,25-27. We will work closely
with Core C (Bioinformatics) to leverage the latest single cell interpretation tools to answer questions
about the various cell states identified and their relationship to aging perturbations.

## Key facts

- **NIH application ID:** 10768508
- **Project number:** 2P01AG036695-12A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Sean Curtis Bendall
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $273,757
- **Award type:** 2
- **Project period:** 2011-07-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10768508

## Citation

> US National Institutes of Health, RePORTER application 10768508, Molecular Regulation of Stem Cell Aging (2P01AG036695-12A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10768508. Licensed CC0.

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