# Using spatial, single-cell genomic recording to investigate age-associated clonal hematopoiesis

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $525,137

## Abstract

Project Summary:
Hematopoiesis primarily takes place within the dense milieu of the bone marrow. It is regulated by complex
signaling interactions among multiple cell types to maintain a balanced blood pool and to respond to injuries
such as bleeding and infection. During aging, hematopoiesis declines and develops clonal dominance, also
known as clonal hematopoiesis, where a small number of hematopoietic stem and progenitor cells (HSPCs)
produce a disproportionately large amount of blood cells. Clonal hematopoiesis has been associated with
various types of hematologic disorders including leukemia. To understand how and why clonal hematopoiesis
develops with age, it is crucial to examine the key intercellular communications that regulate hematopoiesis
within the bone marrow. This is particularly important because of dramatic age-associated changes to the bone
marrow where the cell number substantially decreases and the cell type composition massively shifts, leading
to changes in the intercellular signaling network critical for hematopoiesis. Here, we will apply a new genomic
recording and imaging technique, MEMOIR (Memory through Enhanced Mutagenesis with Optical In-situ
Readout), to analyze how the aging bone marrow environment alters HSPC intercellular signaling and
influences clonal hematopoiesis. We will test two opposite hypotheses: (1) clonal hematopoiesis is induced by
age-associated changes to the intercellular signaling of HSPCs in the bone marrow; and alternatively (2) clonal
hematopoiesis is the result of intrinsic changes in HSPCs that allow them to escape from the control of the
intercellular signaling network. We will determine how aging alters the spatial context and intercellular signaling
of HSPCs, and influences their clonal expansion. And we will investigate how age-associated spontaneous
mutations perturb the spatial context and intercellular signaling of HSPC clonal expansion. Our proposed study
will identify the lineage relationships and spatial organization of individual HSPCs as well as their intercellular
signaling in the aging bone marrow. Our results can reveal new cellular and molecular players underlying
clonal hematopoiesis that could be used as therapeutic targets to control hematopoietic aging and age-related
diseases. More generally, this study will provide an experimental and conceptual framework for analyzing
spatially defined intercellular communication in hematopoiesis.

## Key facts

- **NIH application ID:** 10809020
- **Project number:** 5R01AG080982-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** MICHAEL B ELOWITZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $525,137
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809020

## Citation

> US National Institutes of Health, RePORTER application 10809020, Using spatial, single-cell genomic recording to investigate age-associated clonal hematopoiesis (5R01AG080982-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10809020. Licensed CC0.

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