美国麻省理工学院和哈佛大学博德研究所Gökhan S. Hotamlgil课题组在研究中取得进展。他们揭示了肝脏亚细胞结构调控代谢稳态。相关论文于2022年3月9日发表在《自然》杂志上。

他们使用增强的聚焦离子束以高分辨率（8 nm 各向同性像素大小）解析了大体积（超过 2.8 × 105 µm3）完整肝组织（每种条件 15 个部分或全部肝细胞）中细胞器的三维结构组织扫描电子显微镜成像，然后是基于深度学习的自动图像分割和 3D 重建。他们还对瘦小鼠和肥胖小鼠的肝组织中的亚细胞结构进行了比较分析，发现了实质性的改变，特别是在肝内质网 (ER) 中，它经历了大规模的结构重组。

最后，他们通过监测亚细胞组织的实验性恢复对细胞和全身代谢的影响，证明了这些结构变化的功能重要性。他们得出结论，ER 结构的肝亚细胞组织是高度动态的，与代谢状态相结合，对适应性稳态和组织健康至关重要。

据悉，细胞通过将代谢过程划分为细胞器来显示复杂的细胞内组织，但这些结构在天然组织环境中的分辨率及其功能后果尚不清楚。

附：英文原文

Title: Regulation of liver subcellular architecture controls metabolic homeostasis

Author: Parlakgl, Gne, Arruda, Ana Paula, Pang, Song, Cagampan, Erika, Min, Nina, Gney, Ekin, Lee, Grace Yankun, Inouye, Karen, Hess, Harald F., Xu, C. Shan, Hotamlgil, Gkhan S.

Issue&Volume: 2022-03-09

Abstract: Cells display complex intracellular organization by compartmentalization of metabolic processes into organelles, yet the resolution of these structures in the native tissue context and their functional consequences are not well understood. Here we resolved the three-dimensional structural organization of organelles in large (more than 2.8 × 105 µm3) volumes of intact liver tissue (15 partial or full hepatocytes per condition) at high resolution (8 nm isotropic pixel size) using enhanced focused ion beam scanning electron microscopy1,2 imaging followed by deep-learning-based automated image segmentation and 3D reconstruction. We also performed a comparative analysis of subcellular structures in liver tissue of lean and obese mice and found substantial alterations, particularly in hepatic endoplasmic reticulum (ER), which undergoes massive structural reorganization characterized by marked disorganization of stacks of ER sheets3 and predominance of ER tubules. Finally, we demonstrated the functional importance of these structural changes by monitoring the effects of experimental recovery of the subcellular organization on cellular and systemic metabolism. We conclude that the hepatic subcellular organization of the ER architecture are highly dynamic, integrated with the metabolic state and critical for adaptive homeostasis and tissue health. Detailed reconstruction using enhanced focused ion beam scanning electron microscopy imaging and deep-learning-based automated segmentation demonstrates that hepatocyte subcellular organelle architecture regulates metabolism.

DOI: 10.1038/s41586-022-04488-5

Source: https://www.nature.com/articles/s41586-022-04488-5