# Identification of a mesenchymal progenitor cell hierarchy in adipose tissue

> **NIH NIH K08** · UNIVERSITY OF PENNSYLVANIA · 2020 · $167,940

## Abstract

PROJECT TITLE
Characterization of a novel adipogenic mesenchymal progenitor population inhabiting a unique interstitial
tissue niche.
ABSTRACT
Obesity and the associated metabolic syndrome represent a profound public health challenge for which there
are few effective therapeutics. Fundamentally, obesity arises in the setting of nutrient excess, which stimulates
adipose tissue expansion. The healthy growth of adipose tissue depends on the capacity of progenitor cells to
undergo de novo adipogenesis. However, the cellular hierarchy and mechanisms governing adipocyte
progenitor differentiation are poorly understood.
Adipose mesenchymal progenitors represent a complex pool of highly diverse cell types, and previous
attempts to characterize these populations using candidate gene approaches have been significantly limited by
lack of specificity and loss of spatial information. Using unbiased single-cell RNA transcriptomics coupled with
immunohistochemistry, we identified a novel progenitor population which we term Interstitial Progenitor Cells
(IPCs). IPCs are multipotent progenitors, marked by expression of Dpp4 and Wnt2, which can give rise to
committed preadipocytes and mature adipocytes. Importantly, we show that IPCs inhabit the Reticular
Interstitium (RI), a fibrous tissue that envelops many organs including adipose depots and represents a
previously unrecognized anatomical niche for multipotent mesenchymal progenitors.
The scientific objectives of this proposal are to determine the in vivo contribution of IPCs to adipose tissue
biology and define the niche elements that maintain IPC identity and direct lineage allocation. The Aims of the
proposal are: 1) Trace the in vivo lineage allocation of IPCs during early adipose organogenesis and adult
stimulated adipogenesis. 2) Investigate the role of TGFβ and Wnt signaling in IPC maintenance and
differentiation. In addition to the scientific contributions of the proposed aims, this proposal outlines a
structured, focused training plan that will equip me with the techniques and expertise in progenitor cell biology
that will serve as the foundation of a successful transition to independence.

## Key facts

- **NIH application ID:** 9977190
- **Project number:** 5K08DK122099-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** David Michael Merrick
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $167,940
- **Award type:** 5
- **Project period:** 2019-07-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977190

## Citation

> US National Institutes of Health, RePORTER application 9977190, Identification of a mesenchymal progenitor cell hierarchy in adipose tissue (5K08DK122099-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9977190. Licensed CC0.

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