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依赖于BBS8的状刺信号控制了白色脂肪组织中的细胞命运

Katharina Sieckmann¹, Nora Winnerling¹, Dalila Juliana Silva Ribeiro¹

¹Institute of Innate Immunity, Biophysical Imaging, Medical Faculty, University of Bonn, Bonn, Germany.

The EMBO journal

|August 20, 2025

概括

巴德特-比德尔综合征 (BBS) 中的初级毛功能障碍扰乱了脂肪细胞前体细胞 (APC) 的命运,促进纤维化而不是脂肪的发展,并导致肥胖. 这突出了乳毛.

科学领域:

细胞生物学细胞生物学
代谢疾病代谢疾病
肥胖问题研究研究

背景情况:

初级毛是细胞信号传递和全身能量代谢的关键调节者.
正如巴德特-比德尔综合征 (BBS) 中所见的那样,初级乳毛的功能障碍与肥胖,过和白脂肪组织 (WAT) 改造有关.

研究的目的:

研究一次性乳毛在调节脂肪细胞前体细胞 (APC) 命运和肥胖期间的分化中的作用.
阐明原发性乳毛功能障碍影响WAT平衡的分子机制.

主要方法:

使用了Bbs8^-/-小鼠,以模拟BBS表型.
采用单细胞RNA测序来分析APC亚群及其分化途径.
研究了在APC命运决定中的状刺信号的作用.

主要成果:

在Bbs8^-/-小鼠中,原发性乳毛损失减少了类似干细胞的P1 APC亚群,诱导了转向纤维原始细胞的转换.
在APC中观察到细胞外矩阵重塑和增加CD9表达,纤维化标志物,在肥胖发作之前.
单细胞RNA测序证实了直接的APC过渡到纤维基原体,绕过正常分化阶段.
在Bbs8^-/-中的异卵性状刺信号APCs改变了脂肪细胞的分化和脂质的吸收.

结论:

主要毛控制APC的命运,平衡脂肪生成和纤维生成.
主要毛功能障碍促进了APC中的纤维原生原生体状态,导致肥胖.
这些发现确定了初级乳毛作为肥胖和相关代谢障碍的新治疗.

关键词:

脂肪组织脂肪组织 BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS BBS 细胞命运细胞命运西里亚 (Cilia) 是一个小体.

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