Bui Hoang, Hansen Julia K, Lo Sardo Valentina, Galmozzi Andrea
Department of Medicine, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI.
Nutrition and Metabolism Graduate Program, University of Wisconsin-Madison, Madison, WI.
bioRxiv. 2025 May 30:2025.05.28.656577. doi: 10.1101/2025.05.28.656577.
Adipose tissue heterogeneity has emerged as a central factor in regulating adipose tissue function in physiology and pathophysiology, yet tools to model and study this diversity remain limited. Here, we performed single-cell RNA sequencing on cultured primary white and brown preadipocytes to assess how conditions impact progenitor identity. We identified two major subpopulations in both depots: committed adipogenic precursors (CAPs) and fibro-adipogenic progenitor-like cells (FAPLs). Remarkably, FAPLs were also present in brown adipose tissue, expanding the known landscape of progenitor populations in this depot. Trajectory and regulon analyses revealed that both white and brown FAPLs exhibit similar pro-fibrotic, stress-responsive signatures and diverge early from proliferating progenitor states. Integration of datasets showed that FAPLs from both depots cluster together, emphasizing their conserved identity, while CAPs remain depot-specific. Comparison to previously published single-cell datasets revealed that these populations, including brown adipose FAPLs, correspond to adipose-resident progenitor subtypes, validating the physiological relevance of this model for studying adipose tissue heterogeneity and development.
脂肪组织异质性已成为调节生理和病理生理过程中脂肪组织功能的核心因素，但用于模拟和研究这种多样性的工具仍然有限。在这里，我们对培养的原代白色和棕色前脂肪细胞进行了单细胞RNA测序，以评估不同条件如何影响祖细胞特性。我们在两个脂肪库中都鉴定出了两个主要亚群：定向脂肪生成前体（CAPs）和成纤维脂肪生成祖细胞样细胞（FAPLs）。值得注意的是，FAPLs也存在于棕色脂肪组织中，扩展了该脂肪库中已知的祖细胞群体格局。轨迹和调控子分析表明，白色和棕色FAPLs均表现出相似的促纤维化、应激反应特征，并且在早期就与增殖的祖细胞状态分化。数据集整合显示，来自两个脂肪库的FAPLs聚集在一起，强调了它们保守一致的特性，而CAPs则保持脂肪库特异性。与之前发表的单细胞数据集比较表明，这些群体，包括棕色脂肪FAPLs，对应于脂肪组织驻留祖细胞亚型，验证了该模型在研究脂肪组织异质性和发育方面的生理相关性。
