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嗜铬细胞瘤患者的脂肪组织可塑性表明剪接机制在人类脂肪棕色化中发挥作用。

Adipose tissue plasticity in pheochromocytoma patients suggests a role of the splicing machinery in human adipose browning.

作者信息

Castellá Moisés, Blasco-Roset Albert, Peyrou Marion, Gavaldà-Navarro Aleix, Villarroya Joan, Quesada-López Tania, Lorente-Poch Leyre, Sancho Juan, Szymczak Florian, Piron Anthony, Rodríguez-Fernández Sonia, Carobbio Stefania, Goday Albert, Domingo Pere, Vidal-Puig Antonio, Giralt Marta, Eizirik Décio L, Villarroya Francesc, Cereijo Rubén

机构信息

Departament de Bioquímica i Biomedicina Molecular, Universitat de Barcelona; Institut de Biomedicina de la Universitat de Barcelona (IBUB); and Institut de Recerca de Sant Joan de Déu, 08028 Barcelona, Spain.

CIBER Fisiopatología de la Obesidad y Nutrición, 28029 Madrid, Spain.

出版信息

iScience. 2023 May 9;26(6):106847. doi: 10.1016/j.isci.2023.106847. eCollection 2023 Jun 16.

DOI:10.1016/j.isci.2023.106847
PMID:37250773
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10209542/
Abstract

Adipose tissue from pheochromocytoma patients acquires brown fat features, making it a valuable model for studying the mechanisms that control thermogenic adipose plasticity in humans. Transcriptomic analyses revealed a massive downregulation of splicing machinery components and splicing regulatory factors in browned adipose tissue from patients, with upregulation of a few genes encoding RNA-binding proteins potentially involved in splicing regulation. These changes were also observed in cell culture models of human brown adipocyte differentiation, confirming a potential involvement of splicing in the cell-autonomous control of adipose browning. The coordinated changes in splicing are associated with a profound modification in the expression levels of splicing-driven transcript isoforms for genes involved in the specialized metabolism of brown adipocytes and those encoding master transcriptional regulators of adipose browning. Splicing control appears to be a relevant component of the coordinated gene expression changes that allow human adipose tissue to acquire a brown phenotype.

摘要

嗜铬细胞瘤患者的脂肪组织具有棕色脂肪特征，使其成为研究人类产热脂肪可塑性调控机制的宝贵模型。转录组分析显示，患者棕色化脂肪组织中剪接机制成分和剪接调节因子大量下调，而一些编码可能参与剪接调节的RNA结合蛋白的基因上调。在人类棕色脂肪细胞分化的细胞培养模型中也观察到了这些变化，证实剪接可能参与脂肪棕色化的细胞自主调控。剪接的协同变化与棕色脂肪细胞特殊代谢相关基因以及编码脂肪棕色化主要转录调节因子的基因的剪接驱动转录异构体表达水平的深刻改变有关。剪接控制似乎是使人类脂肪组织获得棕色表型的协同基因表达变化的一个相关组成部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b46/10209542/4a8e533c95db/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b46/10209542/242b12bedcb2/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b46/10209542/05ab0bb40f8f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b46/10209542/cf0505a150aa/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b46/10209542/1646a3436ee7/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b46/10209542/28f0940bfa70/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b46/10209542/166d73106ceb/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b46/10209542/4a8e533c95db/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b46/10209542/242b12bedcb2/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b46/10209542/05ab0bb40f8f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b46/10209542/cf0505a150aa/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b46/10209542/1646a3436ee7/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b46/10209542/28f0940bfa70/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b46/10209542/166d73106ceb/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b46/10209542/4a8e533c95db/gr6.jpg

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本文引用的文献

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Biomedicines. 2022 Mar 2;10(3):586. doi: 10.3390/biomedicines10030586.
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A single-cell atlas of human and mouse white adipose tissue.人类和小鼠白色脂肪组织的单细胞图谱
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Beige Adipocyte as the Flame of White Adipose Tissue: Regulation of Browning and Impact of Obesity.米色脂肪细胞作为白色脂肪组织的火焰：褐色化的调节及肥胖的影响
关键生热基因在人褐色脂肪细胞中的异构体表达。
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The RNA-Binding Protein HuD Regulates Alternative Splicing and Alternative Polyadenylation in the Mouse Neocortex.RNA 结合蛋白 HuD 调控小鼠新皮层中的可变剪接和可变多聚腺苷酸化。
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