# Acetate as a Mediator of Hematopoietic Stem Cell Inflammatory Response and Clonal Hematopoiesis

> **NIH NIH F31** · BAYLOR COLLEGE OF MEDICINE · 2022 · $46,752

## Abstract

PROJECT SUMMARY
Hematopoietic stem and progenitor cells (HSPCs) are responsible for the maintenance and regeneration of the
adult hematopoietic system. These cells are responsive to systemic cues that influence their differentiation, such
as inflammation, in the form of cytokines such as interferons and interleukins. Inflammation is particularly
noteworthy for its influence not only in normal hematopoiesis, but as a driver of clonal hematopoiesis (CH), the
overrepresentation of specific mutant clones in the hematopoietic system. Mutations in Tet2 represent a common
driver of CH, and Tet2 mutant HSPCs expand preferentially in response to inflammatory stimuli. Recently,
acetate has been implicated as an inflammation-associated metabolic signal. Acetate rises systemically during
inflammation but is also elevated as a byproduct of dietary components, particularly fructose. I have found in
preliminary studies that supplementing acetate, either directly or through fructose, along with inflammatory stimuli
broadly exacerbates inflammation in the form of inflammatory serum cytokines and HSPC inflammatory gene
expression. Together, these results suggest a role for acetate as a diet-associated metabolic mediator of
inflammation, relevant to both normal and clonal hematopoiesis. Therefore, the focus of this proposal is to 1)
interrogate the hematopoietic response to changes in systemic acetate levels during inflammation and to 2)
interrogate acetate as a driver of clonal hematopoiesis during inflammation. These aims will be accomplished
through a combination of functional, gene expression, and phenotypic studies of HSPCs in response to acetate
during inflammation.

## Key facts

- **NIH application ID:** 10464508
- **Project number:** 1F31HL164097-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** JONATHAN TIESSEN
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464508

## Citation

> US National Institutes of Health, RePORTER application 10464508, Acetate as a Mediator of Hematopoietic Stem Cell Inflammatory Response and Clonal Hematopoiesis (1F31HL164097-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10464508. Licensed CC0.

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