Igf2 regulates early postnatal DPP4⁺ preadipocyte pool expansion

Area of Science:

• Cell Biology
• Metabolism
• Developmental Biology

Background:

• Adipose tissue expansion is a critical early-life process.
• Understanding the mechanisms of adipose tissue development is key to addressing obesity.
• Metabolically healthy obesity requires elucidation of adipose tissue expansion cues.

Purpose of the Study:

• To identify cellular and molecular drivers of early-life adipose tissue expansion.
• To investigate the role of specific progenitor cells in subcutaneous adipose tissue development.
• To understand the function of insulin growth factor 2 (IGF2) in preadipocyte biology.

Main Methods:

• Single-cell RNA sequencing of murine subcutaneous adipose tissue from prewean and adult mice.
• Identification and characterization of specific progenitor cell populations.
• Genetic manipulation to assess the role of IGF2 in Dpp4+ progenitor cells.

Main Results:

• A novel dipeptidyl peptidase-4 (Dpp4)-positive progenitor cell population was identified in prewean mice.
• These Dpp4+ progenitors express insulin growth factor 2 (IGF2).
• IGF2 signaling in these cells promotes proliferation over differentiation, and its loss enhances adipogenesis.

Conclusions:

• Temporally restricted IGF2 expression in Dpp4+ progenitor cells is a key driver of early-life adipose tissue expansion.
• This mechanism highlights a specific pathway regulating preadipocyte proliferation during development.
• Findings contribute to understanding the basis of metabolically healthy obesity.