Decreased blood vessel density and endothelial cell subset dynamics during ageing of the endocrine system.
Decreased blood vessel density and endothelial cell subset dynamics during ageing of the endocrine system.
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DOI：
10.15252/embj.2020105242
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发表时间：
2021-01-04
期刊：
影响因子：
--
通讯作者：
Kusumbe AP
中科院分区：
文献类型：
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作者：
Chen J;Lippo L;Labella R;Tan SL;Marsden BD;Dustin ML;Ramasamy SK;Kusumbe AP
与年龄相关的激素分泌内分泌系统的改变会导致器官功能障碍和疾病状态。然而，内分泌组织衰老的细胞生物学仍然知之甚少。在这里，我们进行比较3D成像，以了解内分泌腺中内皮细胞（EC）室的年龄相关扰动。一系列广泛的标志物数据集强调了毛细血管和动脉数量的下降，但不是胰腺，睾丸和甲状腺中的血管周围细胞，随着小鼠和人类的年龄增长。此外，胰腺中的血管生成和β细胞扩增与EC的不同年龄依赖性子集相结合。虽然该EC亚群支持胰腺β细胞，但其在衰老过程中随着差距连接蛋白Gja 1的表达增加而下降。EC特异性消融Gja 1可恢复老年胰腺中的β细胞扩增。这些结果为理解年龄相关的血管变化提供了概念证明，并暗示血管靶向治疗可能恢复老化的内分泌组织功能。这本全面的数据地图集提供了超过1,000册的彩色书籍，用于内分泌学、衰老、基质和血管生物学的探索和研究。单细胞分辨率3D成像揭示了激素分泌腺血管系统中基于器官的专业化和年龄相关的变化。
Age‐associated alterations of the hormone‐secreting endocrine system cause organ dysfunction and disease states. However, the cell biology of endocrine tissue ageing remains poorly understood. Here, we perform comparative 3D imaging to understand age‐related perturbations of the endothelial cell (EC) compartment in endocrine glands. Datasets of a wide range of markers highlight a decline in capillary and artery numbers, but not of perivascular cells in pancreas, testis and thyroid gland, with age in mice and humans. Further, angiogenesis and β‐cell expansion in the pancreas are coupled by a distinct age‐dependent subset of ECs. While this EC subpopulation supports pancreatic β cells, it declines during ageing concomitant with increased expression of the gap junction protein Gja1. EC‐specific ablation of Gja1 restores β‐cell expansion in the aged pancreas. These results provide a proof of concept for understanding age‐related vascular changes and imply that therapeutic targeting of blood vessels may restore aged endocrine tissue function. This comprehensive data atlas offers over > 1,000 multicolour volumes for exploration and research in endocrinology, ageing, matrix and vascular biology. Single‐cell‐resolution 3D imaging unveils organ‐based specialisation and age‐related changes in the vasculature of hormone‐secreting glands.