Brown adipose tissue involution associated with progressive restriction in progenitor competence.
Brown adipose tissue involution associated with progressive restriction in progenitor competence.
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DOI：
10.1016/j.celrep.2022.110575
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发表时间：
2022-04-12
期刊：
影响因子：
8.8
通讯作者：
Ruan, Hai-Bin
中科院分区：
文献类型：
--
作者：
Huang, Zan;Zhang, Zengdi;Moazzami, Zahra;Heck, Ryan;Hu, Ping;Nanda, Hezkiel;Ren, Kaiqun;Sun, Zequn;Bartolomucci, Alessandro;Gao, Yan;Chung, Dongjun;Zhu, Weiyun;Shen, Steven;Ruan, Hai-Bin
人类棕色脂肪组织（BAT）经历进行性退化。这种对合过程在啮齿类动物中没有重现，潜在的机制也知之甚少。本研究表明，家兔的肩胛骨间区（iBAT）在成年早期迅速变白。成熟脂肪细胞的转录组重塑和身份转换伴随着祖细胞褐脂肪生成能力的丧失。单细胞RNA测序显示兔和人iBAT祖细胞高度表达FSTL1基因。当iBAT在家兔中发挥作用时，脂肪细胞祖细胞会降低FSTL1的表达，并且对褐色脂肪的募集难以耐受。相反，FSTL1在小鼠iBAT中组成性表达，以维持WNT信号传导并防止退化。通过Fstl1基因的基因缺失或Fstl1+祖细胞的消融，可以诱导小鼠的祖细胞功能不全和iBAT缺失。我们的研究结果强调了BAT祖细胞室的层次结构和动力学，并暗示表达fstl1的祖细胞在BAT退化中功能不全。针对棕色脂肪组织（BAT）对抗代谢疾病的一个挑战是缺乏对人类年龄依赖性BAT退化的调节知识。Huang等人以家兔为模型，提出表达fstl1的脂肪细胞祖细胞的功能限制有助于BAT退化。
Human brown adipose tissue (BAT) undergoes progressive involution. This involution process is not recapitulated in rodents, and the underlying mechanisms are poorly understood. Here we show that the interscapular BAT (iBAT) of rabbits whitens rapidly during early adulthood. The transcriptomic remodeling and identity switch of mature adipocytes are accompanied by loss of brown adipogenic competence of progenitors. Single-cell RNA sequencing reveals that rabbit and human iBAT progenitors highly express the FSTL1 gene. When iBAT involutes in rabbits, adipocyte progenitors reduce FSTL1 expression and are refractory to brown adipogenic recruitment. Conversely, FSTL1 is constitutively expressed in mouse iBAT to sustain WNT signaling and prevent involution. Progenitor incompetence and iBAT paucity can be induced in mice by genetic deletion of the Fstl1 gene or ablation of Fstl1+ progenitors. Our results highlight the hierarchy and dynamics of the BAT progenitor compartment and implicate the functional incompetence of FSTL1-expressing progenitors in BAT involution. One challenge for targeting brown adipose tissue (BAT) to combat metabolic diseases is a lack of knowledge of the regulation of age-dependent BAT involution in humans. Using rabbits as a model, Huang et al. propose that the functional restriction of FSTL1-expressing adipocyte progenitors contributes to BAT involution.
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影响因子：
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