# Hox genes regulate functionally distinct, regionally restricted MSC populations

> **NIH NIH R33** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $403,491

## Abstract

ABSTRACT
 Multipotent mesenchymal stem/stromal cells (MSCs) are used in a large number of
regenerative/reparative clinical applications and tissue engineering approaches. Translational
outcomes from the use of these cells in various contexts vary widely and generating new
musculoskeletal tissue that is both functional and able to integrate appropriately in vivo remains
a major challenge. Recent research from several laboratories have refined and advanced the
field's ability to enrich for MSCs/stromal cells with high progenitor potential, but a recent study
from my laboratory reveals that MSCs from the bone marrow of different bones of the adult
skeleton maintain the regionally restricted, unique Hox expression profile that is established
during development (Rux, et al., Dev. Cell, 2016). Hox expression is only observed in
progenitor-enriched MSC populations (PDGFRα+/CD51+, LepR-Cre labeled) and is not
detected in differentiated skeletal cell types or in non-progenitor enriched (LepR-negative) non-
endothelial stroma. Further, fracture repair studies demonstrate that Hox11 genes function in
the central limb regions (zeugopod: radius/ulna, tibia/fibula) in adult MSC populations and loss
of Hox11 function leads to the inability of MSC progenitors to differentiate towards cartilage and
bone (but has no effect on adipose differentiation). This leads to the broader question of
whether unique Hox expression patterns in MSCs are a by-product of development and function
via a common mechanism after developmental patterning stages to promote general MSC
potential. Alternatively, the much more interesting and biologically significant possibility is that
unique Hox genes or paralogs may function differentially in spatially distinct MSCs to provide
region-specific regulatory information during growth, maintenance and repair through adult
stages. This has critical implications for the use of MSCs in musculoskeletal tissue engineering
and regenerative approaches as the unique functional and regulatory characteristics of MSCs
may differ considerably depending on their origin; this could profoundly impact their
performance in clinical and tissue engineering applications.

## Key facts

- **NIH application ID:** 10197314
- **Project number:** 4R33AR073523-03
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Deneen M Wellik
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $403,491
- **Award type:** 4N
- **Project period:** 2019-03-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197314

## Citation

> US National Institutes of Health, RePORTER application 10197314, Hox genes regulate functionally distinct, regionally restricted MSC populations (4R33AR073523-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10197314. Licensed CC0.

---

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