Abstract
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.
Highlights
The vascular network functions as a critical regulator of vertebrate physiology through its well-established function of nutrient and oxygen transport
We performed deep imaging followed by computational surface rendering to generate datasets of whole young (2–8 weeks old) and aged (56–70 weeks old) mouse adrenal gland, ovary, pituitary gland, testis, pancreas and thyroid gland (Fig 1A)
The exemplar images show that the organization, expression patterns and spatial distributions of endothelial cell (EC) and other cell types such as pericytes and stromal cells are evident in our 3D volumes (Fig 1A and Movies EV1– EV11) enabling the generation of cellular cartography for these cell types across the endocrine system
Summary
The vascular network functions as a critical regulator of vertebrate physiology through its well-established function of nutrient and oxygen transport. Tissue-specific capillary beds support a distinctive function of each organ and respond to dynamically changing local needs (Nolan et al, 2013; Rafii et al, 2016; Augustin & Koh, 2017). This is true for the endocrine system, which provides spatial, rapid and dynamic hormone output in response to systemic and regional changes (Tsang et al, 2016; Nadal et al, 2017; Russell & Lightman, 2019). A systematic understanding of age-dependent changes in tissue microenvironments of endocrine glands remains elusive
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