# Role of ARID3a in aging human hematopoietic progenitor cells

> **NIH NIH R00** · EAST CAROLINA UNIVERSITY · 2021 · $244,945

## Abstract

Project Summary
 Human hematopoiesis is a complex, dynamic process that requires intricate regulation of multiple gene
pathways involved in lineage commitments, leading to development of multiple mature blood cell types.
Multiple studies in mice and humans report age-related defects in early hematopoiesis and functions defects in
the mature aged immune cell populations, which leads to impaired immune responses to pathogens. These
defects are especially important because population studies estimate that nearly 40% of European and US
populations will be over 60 years of age by 2050. Previous studies in our lab indicate that loss of expression of
the DNA-binding protein ARID3a leads to hematopoietic developmental skewing away from lymphoid lineage
progenitors, indicating that ARID3a is important for normal hematopoiesis. Preliminary data from aged human
peripheral blood shows decreased frequency of ARID3a-expressing hematopoietic stem cells (HSCs), leading
to decreased numbers of multipotent progenitors and multi-lymphoid progenitors, but no alterations in numbers
of myeloid progenitor cells when compared to healthy young peripheral blood. The proposed studies seek to
expanded the preliminary phenotypical data of ex vivo young and aged human peripheral blood hematopoietic
progenitor cells for statistical significance, evaluate and compare developmental potential of young ARID3a-
expressing, young ARID3a-deficient and aged HSCs in vitro and in vivo. We will further examine the gene
expression differences between young and old, as well as between ARID3a expressing and ARID3a deficient
HSCs by RNA-seq. Differentially expressed genes will be further analyzed for ARID3a binding and chromatin
remodeling by ChIP-seq and ATAC-seq analyses. These sequencing techniques will be the focus of the
training portion of this proposal. Finally, we will evaluate the capacity of young ARID3a-expressing, young
ARID3a-deficient, and old HSC engrafted humanized mice to mount immune responses to immunization with
PC-KLH and survival following inoculation with S. pneumoniae. The overall goal of the proposed studies is to
determine the effect of ARID3a expression in HSCs on immunosenescence and innate immune responses.
Completion of these studies will stratify HSCs based on ARID3a expression, identify ARID3a-regulated genes
important for aging, and identify potential therapeutic targets for improving immunological function in elderly
individuals.

## Key facts

- **NIH application ID:** 10263295
- **Project number:** 5R00AG055717-04
- **Recipient organization:** EAST CAROLINA UNIVERSITY
- **Principal Investigator:** Michelle Leigh Ratliff
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $244,945
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10263295

## Citation

> US National Institutes of Health, RePORTER application 10263295, Role of ARID3a in aging human hematopoietic progenitor cells (5R00AG055717-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10263295. Licensed CC0.

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