# Metabolic Programming of Hematopoietic Stem Cell Function by Prenatal Folate

> **NIH NIH F31** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $43,481

## Abstract

ABSTRACT
The goal of this project is to determine the effect of prenatal folate status on hematopoietic stem cell (HSC)
establishment and function. The Developmental Origin of Health and Disease (DOHaD) hypothesis purports that
many adult-onset diseases originate during perinatal development. This phenomenon of developmental
programming of disease has since been demonstrated to be mediated at least in part by epigenetic changes
during development, as these effects also occur trans-generationally. Folic acid is a major nutritional component
that regulates cellular methylation and epigenetic patterning during fetal life, and prenatal folate deficiency is
independently associated with failure of neural tube closure. Population-wide folic acid fortification is used in
many parts of the world for the prevention of neural tube defects (NTDs), as approximately 70% of NTDs are
prevented by folate supplementation. We will test the hypothesis that varying prenatal folate status programs
risk for adult-onset disease by altering hematopoietic stem cell function and consequent immune trajectory from
the developmental stage onwards. In this grant we propose that heterogeneity, function, and output of the adult
HSC compartment can be shaped by perturbation during early development. Our previous work on the effects
prenatal inflammation on the developing hematopoietic system show evidence that perturbation during early
development can influence adult hematopoiesis and immune function. We will then apply this idea to test the
effects of varying prenatal folate on hematopoietic establishment. Proliferation, genomic stability, and cell
methylation are all processes influenced by folate-mediated OCM and are known to impact HSC establishment
and function. We believe that early life alterations in folate-mediated OCM are likely to influence long-term HSC
function. The underlying question of how maternal nutrition influences stem cell outcomes is underexplored. Our
preliminary data shows that exposure to varying prenatal folate results in alterations in HSC establishment.
Additionally, our model of prenatal folate metabolically reprograms HSCs during fetal life that persist into
adulthood with altered function. These changes are in part driven by differences in metabolic gene expression.
By examining how prenatal folate alters HSC function, we will be one of the first labs to directly identify the effects
of maternal nutrition on health consequences by affecting the establishment and function of HSCs. In addition to
the research statement contained within, I have developed a training plan that I believe will ensure my success
across all aspects of the proposed research plan. The training plan I have developed not only addresses the
training needs that are specific to this proposal but also builds on my interests that will give me tools to investigate
metabolic programming, integrate “omics” datasets and stitch together multiple fields related to public health.
This tra...

## Key facts

- **NIH application ID:** 10910880
- **Project number:** 5F31HL170732-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Brian Krum
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $43,481
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10910880

## Citation

> US National Institutes of Health, RePORTER application 10910880, Metabolic Programming of Hematopoietic Stem Cell Function by Prenatal Folate (5F31HL170732-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10910880. Licensed CC0.

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