用单细胞测序解析人体脂肪细胞发育轨迹，发现关键信号通路。
Reconstructing the Developmental Trajectory of Adipocytes in Human Adipose Tissue Using Single-Cell RNA Sequencing
- 通过单细胞测序识别15个细胞簇和7个过渡状态，重建脂肪细胞分化过程。
- 发现IGF和FGF通路在分化各阶段持续活跃（p<0.05），主导细胞通讯。
- 揭示内脏与皮下脂肪差异，指出IGF在血管周围、FGF在成熟区富集。
肥胖是与2型糖尿病和心血管疾病相关的全球健康危机。本研究利用单细胞RNA测序重建了人类脂肪组织中脂肪细胞的发育轨迹。分析识别出15个转录特征不同的细胞簇，包括7个过渡状态，揭示了脂肪细胞分化的动态过程。检测到16条功能活跃的信号通路介导脂肪细胞与其前体细胞间的通讯，其中胰岛素样生长因子（IGF）和成纤维细胞生长因子（FGF）通路最为显著，在分化各阶段均保持持续活跃（p<0.05）。研究发现腹腔脂肪细胞存在皮下脂肪所无的额外细胞外基质重塑。空间分析显示，IGF信号在血管周围微环境中尤为活跃，而FGF活动则集中于成熟脂肪细胞区域。该研究首次构建了人类脂肪细胞发育的综合图谱，强调IGF和FGF通路为潜在治疗靶点。识别出的信号网络为促进健康脂肪扩张或抑制病理性脂肪积累提供了新思路。本工作深化了对脂肪组织生物学的基本理解，同时为代谢性疾病治疗提供临床相关数据。
原文摘要 · Abstract (English)
Obesity is a global health crisis associated with metabolic disorders such as type 2 diabetes and cardiovascular disease. This study employed single-cell RNA sequencing to reconstruct the developmental trajectory of human adipocytes from adipose tissue samples. Our analysis identified 15 transcriptionally distinct cell clusters, including 7 transitional states, revealing the dynamic process of adipocyte differentiation. We detected 16 functionally active signaling pathways mediating cellular communication between adipocytes and their progenitors. Among these, insulin-like growth factor (IGF) and fibroblast growth factor (FGF) pathways emerged as the most prominent networks, showing consistent activity across differentiation stages (p<0.05). The study revealed depot-specific differences, with visceral adipocytes undergoing additional extracellular matrix remodeling absent in subcutaneous differentiation. Spatial analysis further showed that IGF signaling was particularly active in perivascular niches, while FGF activity dominated in mature adipocyte zones. These results provide the first comprehensive map of human adipocyte development, highlighting IGF and FGF pathways as potential therapeutic targets. The identified signaling networks offer new insights for developing interventions to promote healthy adipose expansion or inhibit pathological fat accumulation. This work advances our fundamental understanding of adipose tissue biology while providing clinically relevant data for metabolic disorder treatments.
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