# Skeletal Stem Cell PDGFR-beta Signaling as a New Regulator of the HSC Niche

> **NIH NIH F32** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2021 · $70,458

## Abstract

PROJECT SUMMARY/ABSTRACT
Platelet-derived growth factor (PDGF) and its corresponding receptors (PDGFRα and PDGFRβ) regulate
organogenesis and tissue homeostasis. Abnormal receptor signaling has been implicated in developmental
syndromes and adult diseases such as fibrosis, cardiovascular disease, and cancer. Therefore, PDGF receptor
activation and its downstream signaling have been proposed as potential therapeutic targets. Recent reports
have implicated PDGFRβ signaling in regulating bone marrow (BM) microenvironment and hematopoietic stem
cell (HSC) maintenance. Although skeletal stem cells (SSCs) are known to express PDGFRβ, a regulatory role
of PDGFRβ in HSC niche is unknown. Our goal is to determine the roles of PDGFRβ in HSC niche
maintenance and SSC function. Our central hypothesis is that PDGFRβ signaling in SSCs regulates the size of
the HSC niche and blood-forming functions of the BM. With our expertise in PDGF signaling and novel genetic
approaches, this project will address the central hypothesis with the two following aims: 1) Characterize the
impact of SSC PDGFRβ signaling on the HSC pool maintenance and myeloproliferative neoplasia (MPN)
development and 2) Define the functional consequences on SSCs/stromal lineages with altered PDGFRβ
signaling. In Aim 1, tamoxifen-inducible Gli1 Cre recombinase mouse line (Gli1-CreER) will be used to
conditionally induce a gain-of-function PDGFRβ knock-in allele or to inactivate the endogenous Pdgfrb gene in
Gli1+ SSCs. Experiments using WT and mutants will focus on the evaluation of functional changes in BM and
blood with altered PDGFRβ in SSCs. We will transplant BM from PDGFRβ mutants to irradiated wild type (WT)
mice (or vice versa) to determine the extent at which blood forming cells acquire permanent functional
alterations from the PDGFRβ mutant environment. Finally, we will determine whether altered PDGFRβ-
regulated stromal environment alters MPN progression using BM transplantation with JAK2-V617F mutant BM
cells. In Aim 2, in order to characterize cellular changes and functionality in HSC niche-supportive SSCs and
stromal lineages in PDGFRβ mutants, we will use in vitro SSC assays to evaluate functional changes in SSC
stemness, differentiation, and cytokine production. Finally, SSCs sorted from BM of PDGFRβ mutants or
controls will be transplanted into WT kidney capsules to determine the impact of SSC PDGFRβ signaling on
the modulation of BM formation and HSC colonization in vivo. The results of these projects will generate new
knowledge of PDGFRβ signaling-mediated stroma-to-HSC niche crosstalk and facilitate the development of
potential therapeutic targets on BM and hematopoietic diseases.

## Key facts

- **NIH application ID:** 10181025
- **Project number:** 5F32HL142222-03
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** Hae Ryong Kwon
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $70,458
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10181025

## Citation

> US National Institutes of Health, RePORTER application 10181025, Skeletal Stem Cell PDGFR-beta Signaling as a New Regulator of the HSC Niche (5F32HL142222-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10181025. Licensed CC0.

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