# Investigating the Impact of Epigenetic Heterogeneity on Hematopoiesis

> **NIH NIH F31** · UNIVERSITY OF WASHINGTON · 2024 · $48,974

## Abstract

Investigating the Impact of Epigenetic Heterogeneity on Hematopoiesis
Hematopoietic stem cells (HSCs) generate all blood and immune cell types of the body, and proper control of
their self-renewal and differentiation is essential for human health.1,2 Since the work of Till and McCulloch,
heterogeneity has been recognized to be a cardinal feature of HSC biology. Clonally related cells can differ in
their lineage decisions and showed preference towards certain cell fates, even in identical environments.1–6
Researchers termed these skewed decisions as “lineage bias”. Epigenetic mechanisms, such as post-
translational histone modifications (`histone marks'), are postulated to be a possible factor contributing to
individual HSCs heterogeneity and its lineage bias. For example, recent studies suggest that levels of repressive
histone marks at silent gene loci can vary considerably from cell-to-cell and repressive histone marks such as
H3K27me3 can be stably inherited through generations. Since lineage-specifying genes involved in
hematopoiesis are typically held in a repressive state until differentiation, I hypothesize that individual HSCs
show substantial epigenetic state heterogeneity at lineage-specifying gene loci and that this epigenetic
heterogeneity creates stable, heritable lineage biases in these cells. To test this hypothesis, I will determine the
extent of epigenetic heterogeneity present in HSCs, as well as whether it impacts lineage potential for HSCs.
Both of these questions remain unclear due to the lack of methods that can measure epigenetic states consisting
of an array of histone marks and their dynamics within single cells. Recently, the Vaughan and Kueh group
developed a methodology termed Single-Cell Evaluation of Post Translational Epigenetic encoding (SCEPTRE),
which uses super resolution microscopy to resolve and quantify multiple histone marks at specific gene loci of
interest simultaneously. I will use SCEPTRE to investigate the extent of epigenetic heterogeneity present in
HSCs and its descendants (Aim1) first. Then, I will interrogate the heritability and impact of repressive epigenetic
states by coupling SCEPTRE with live-cell tracking (Aim2). If successful, the project will provide an exciting first
look into epigenetic regulation in HSCs at the single-cell level, paving the way for downstream studies to reveal
fundamental aspects of their control and action.

## Key facts

- **NIH application ID:** 10823634
- **Project number:** 1F31HL168825-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Madeline Wong
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10823634

## Citation

> US National Institutes of Health, RePORTER application 10823634, Investigating the Impact of Epigenetic Heterogeneity on Hematopoiesis (1F31HL168825-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10823634. Licensed CC0.

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