在脂肪组织中识别介质前代细胞等级
David Merrick1,2, Alexander Sakers1,2, Zhazira Irgebay1,2
1Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
概括
代谢健康取决于脂肪组织的原始细胞分化为新的脂肪细胞. 研究人员确定了特定的原生细胞类型及其在脂肪组织发育和调节中的作用.
科学领域:
- 细胞生物学
- 代谢健康
- 脂肪生成
背景情况:
- 代谢健康严重依赖于新脂肪生成,即脂肪组织前代细胞分化为成熟脂肪细胞的过程.
- 精确的细胞层次结构和调控机制控制脂肪细胞前代的分化仍然不完全理解.
- 了解这些过程对于解决与脂肪组织功能受损相关的代谢障碍至关重要.
研究的目的:
- 在小鼠和人类脂肪组织中阐明脂肪细胞祖先的细胞层次和分化途径.
- 确定关键的细胞表面标记物和参与脂肪细胞原生体结合和分化的分子调节剂.
- 调查网状间歇体在这些原生细胞的存放中的作用.
主要方法:
- 使用单细胞RNA测序 (scRNA-seq) 来分析脂肪组织前代细胞的转录组形状.
- 细胞表面标记物,包括二基酶-4 (DPP4) / CD26和细胞间粘附分子-1 (ICAM1) / CD54,用于识别不同的原始种群.
- 研究了转化生长因子-β (TGF-β) 信号通路在调节原生细胞身份和分化中的作用.
主要成果:
- scRNA-seq在两种物种的脂肪组织原始体内显示出明显的中酶体细胞层次.
- 鉴定出二基酶-4 (DPP4) / CD26表达细胞是高度增殖的多能原始细胞.
- 这些DPP4+原体分化为表达ICAM1/CD54的承诺前脂肪细胞和表达Clec11a/F3/CD142的脂肪细胞.
- 发现转化生长因子-β 维持了 DPP4+ 的原始性,并抑制了脂肪生成的结合.
- DPP4+原始体被定位到网状间隙,这是一个新发现的组织空间.
结论:
- 脂肪组织的祖先分化遵循一个定义的层次结构,涉及由特定表面蛋白标记的不同的细胞群.
- DPP4+ 细胞是位于网膜间的关键多能原生细胞,对脂肪组织扩张和代谢健康至关重要.
- 在维持原生细胞状态和调节脂肪生成方面,TGF-β信号传递起着至关重要的作用,为代谢疾病提供了潜在的治疗点.
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