# Stress and Human Stem/Progenitor Cells: Biobehavioral Mechanisms

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $650,691

## Abstract

ABSTRACT
Our goal is to test a novel hypothesis in humans about the impact of chronic stress and stress-related biobehavioral processes on
stem/progenitor cell biology. Although substantial progress has been made in understanding how stress becomes biologically
embedded to produce long-term effects, crucial knowledge gaps remain. The processes implicated in biological embed-
ding have been described primarily at the level of differentiated cells types that form tissues and organ systems. Based
on the consideration that the long-term effects of stress can extend well beyond the lifespan of most differentiated
cells, whose replenishment does not occur from already-differentiated ‘parent’ cells, but occurs from stem/progenitor
cells, we advance the hypothesis that biological embedding of the effects of chronic stress may extend all the way down to the level of stem
cells, to define fundamental aspects of their biology that determine the earliest vulnerabilities for common stress- and age-related disorders.
We underscore the importance of studying fetal (newborn) stem cells, focus specifically on hematopoietic (HSCs) and
mesenchymal stem/progenitor cells (MSCs), and on the functional capacity of their telomere and mitochondrial systems as our
primary outcomes. We operationalize chronic stress using a composite biological measure of maternal allostatic load that
incorporates the principal biomarkers of the gestational stress transmission pathway. Because stress responsivity is a key
modulator of chronic stress effects, we additionally propose to characterize this phenotype in HSCs and MSCs via an
in vitro oxidative stress [H2O2] challenge. We will conduct the proposed study in N=300 mother-child dyads; isolate
and culture newborn HSCs and MSCs from umbilical cord blood and cord tissue, respectively; and perform cellular
telomerase activity and high-resolution respirometry experiments to characterize telomere and mitochondrial functional
capacity. Aim 1 will test the hypothesis that chronic stress exposure (allostatic load) is prospectively associated with reduced functional
capacity of newborn HSC and MSC telomere and mitochondrial systems. Aim 2A will test the hypothesis that chronic stress exposure
primes the stress responsivity phenotype of newborn HSCs and MSCs, and Aim 2B will determine whether antioxidant (resveratrol)
pretreatment attenuates this effect. Both aims will include tests for effect modification by sex and key covariates of telomere and
mitochondrial function. Aim 3 will elucidate the maternal sociodemographic, psychosocial, behavioral and biophysical determinants
of variation in components of allostatic load that impact newborn HSC/MSC biology using state-of-the-art machine learning and
prediction approaches. Aim 4 will establish a shared Biobank repository of HSC, MSC, cord blood, cord and placental
tissue samples for future studies of molecular mechanisms (gene expression, epigenetic profiles) and in vitro differen-
tiation. Signi...

## Key facts

- **NIH application ID:** 10684115
- **Project number:** 5R01HD107176-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Kristen Elizabeth Boyle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $650,691
- **Award type:** 5
- **Project period:** 2022-08-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10684115

## Citation

> US National Institutes of Health, RePORTER application 10684115, Stress and Human Stem/Progenitor Cells: Biobehavioral Mechanisms (5R01HD107176-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10684115. Licensed CC0.

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