# Exploring vascular-mesenchymal interactions in the stem cell niche

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $329,925

## Abstract

Project Summary/Abstract
Blood vessels play critical developmental roles in organogenesis related to cellular differentiation, tissue
morphogenesis, and stem cell niches, in addition to delivering oxygen and metabolites to developing tissues.
Dysregulation of vascular development is associated with a number of birth defects and is intimately linked to
tumor progression and metastasis. In spite of these broad human health implications, the mechanisms that
underlie vasculature’s instructive roles in essential biological processes are poorly understood and represent a
major knowledge gap in the field. Our recent work in mice demonstrated that vascular-mesenchymal crosstalk
is a vital process during fetal testis organogenesis. When the male sex determination pathway is triggered in the
presumptive testis, endothelial cells migrate into the testis to form new vascular networks. Interestingly, vascular
remodeling does not occur in the ovary at the same developmental stage. It has been proposed that Sertoli cells,
the supporting cells of the testis, are the main drivers of testis organogenesis, but our recent work showed that
vascular-mesenchymal interactions are a critical morphogenetic force in testis formation. Whether instructive
roles for vasculature exist in other contexts in the fetal testis is unclear. Our preliminary data reveal a novel role
for testicular vasculature in maintaining progenitors for Leydig cells (LCs), which are steroidogenic cells in the
testis interstitial compartment required for the production of testosterone, a critical hormone for sexual
differentiation and adult fertility. When we blocked vascular development of the early fetal testis, supernumerary
LCs differentiated and fewer progenitor cells were maintained, strongly suggesting that blood vessels are a
critical component of the LC niche. However, the molecular and cellular underpinnings of vasculature’s
instructive capacity are unknown. Our long-term goals are to understand which cell types are essential for
maintaining the LC niche and to uncover the molecular signals that regulate LC differentiation. We will test our
central hypothesis that vascular-mesenchymal crosstalk is required for the establishment and maintenance of
the LC niche through 2 specific aims: 1) to delineate the cell types that comprise the vascular niche required for
the establishment and maintenance of LC progenitors; and 2) to elucidate the molecular mechanisms underlying
endothelial-progenitor interactions within the LC niche, focusing on Notch signaling between endothelial cells
and interstitial mesenchyme. To accomplish these aims, we will employ: in vivo genetic mouse models; ex vivo
whole organ culture systems; in vitro primary cell co-culture techniques; and whole organ time-lapse live imaging.
These approaches will allow us to uncover key molecular signals and cellular players that underlie vasculature’s
vital developmental role in a tissue stem cell niche, which we anticipate will have di...

## Key facts

- **NIH application ID:** 9975009
- **Project number:** 5R01HD094698-03
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Tony J. DeFalco
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $329,925
- **Award type:** 5
- **Project period:** 2018-09-24 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975009

## Citation

> US National Institutes of Health, RePORTER application 9975009, Exploring vascular-mesenchymal interactions in the stem cell niche (5R01HD094698-03). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/9975009. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*