Parallel Lineage-Tracing Studies Establish Fibroblasts as the Prevailing In Vivo Adipocyte Progenitor

Area of Science:

• Cell Biology
• Adipogenesis Research
• Vascular Niche Studies

Background:

• The origin of adipocyte progenitor cells within the vascular niche is a long-standing debate.
• Previous studies have inconsistently attributed adipogenic potential to various vascular cell types.
• Clarifying the progenitor cell identity is crucial for understanding adipose tissue development and metabolic diseases.

Purpose of the Study:

• To definitively identify the progenitor cell responsible for de novo adipogenesis within the vascular niche.
• To resolve controversies regarding the contribution of different vascular cell lineages to fat cell formation.
• To elucidate the differentiation pathway of adipocyte progenitor cells.

Main Methods:

• Utilized Cre recombinase-mediated lineage tracing to label distinct vascular cell populations.
• Conducted parallel experiments across multiple adipose tissue depots and conditions.
• Performed histological analyses to examine cell markers and tissue architecture.

Main Results:

• Endothelial and mural cells rarely contribute to new adipocyte formation.
• Platelet-derived growth factor receptor alpha (PDGFRα)-expressing adventitial/capsular fibroblasts are a major source of de novo adipocytes.
• Fibroblasts appear to transition through a beige adipocyte intermediate before maturing into white adipocytes.
• Adipose tissue fibroblasts co-express the mural cell marker PDGFRβ.

Conclusions:

• Adventitial fibroblasts are the primary progenitor cells for adipogenesis in vivo.
• A novel differentiation pathway involving intermediate beige adipocytes is proposed for fibroblast-derived adipocytes.
• These findings reconcile conflicting data and have significant implications for obesity and related metabolic disorders.