# Illuminating adipo-osteoprogenitors in the bone marrow

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2024 · $461,864

## Abstract

Abstract
The bone marrow in mammals house both hematopoietic and mesenchymal cells that are responsible for
sustaining blood and bone cell production, respectively, throughout adult life. Although the hematopoietic
system is well understood, the molecular identities, hierarchy of the marrow mesenchymal cells and their
respective contribution to bone homeostasis are just beginning to be unraveled. Elucidation of the organization
and functions of the bone marrow mesenchymal cells is fundamental to understanding the pathogenesis of
both myeloid and bone diseases. By employing single-cell RNA sequencing (scRNA-seq) technology, we have
discovered a subset of bone marrow mesenchymal cells co-expressing adiponectin (Adipoq) and osterix (Osx)
which are traditionally considered adipocyte or osteoblast markers, respectively. Trajectory analyses predict
the Adipoq+Osx+ bi-marker cells to be common progenitors for osteoblasts and marrow adipogenic lineage
cells. Lineage tracing with Osx-CreERT2 or Adipoq-CreERT2 supports that the bi-marker cells give rise to both
osteoblasts and adipocytes in vivo. Imaging studies localize the bi-marker cells to the endosteal bone niche.
The data therefore support the hypothesis that Adipoq+Osx+ bi-marker cells are adipo-osteoprogenitors attuned
to the physiological milieu in the bone marrow. To test the hypothesis, we will first determine the number and
fate of the bi-marker cells in young, mature and aged mice to uncover potential age-dependent changes (aim
1). We will then investigate the functional contribution of the bi-marker progenitors to bone formation both
under basal conditions and in response to the main bone anabolic drug teriparatide in mature adult mice
(aim2). We will finally examine the effect of diabetes on the fate of the bi-marker cells in an experimentally
induced type II diabetes mouse model. The studies are expected to shed light on the role of the adipo-
osteoprogenitors in bone physiology and pathophysiology.

## Key facts

- **NIH application ID:** 10767985
- **Project number:** 5R01AG077911-02
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Fanxin Long
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $461,864
- **Award type:** 5
- **Project period:** 2023-02-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10767985

## Citation

> US National Institutes of Health, RePORTER application 10767985, Illuminating adipo-osteoprogenitors in the bone marrow (5R01AG077911-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10767985. Licensed CC0.

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