Single‐cell transcriptomes reveal characteristic features of cell types within the human adrenal microenvironment

Abstract

Various cells within the adrenal microenvironment are important in maintaining the body homeostasis. However, our understanding of adrenal disease pathogenesis is limited by an incomplete molecular characterization of the cell types responsible for the organ's multiple homeostatic functions. We report a cellular landscape of the human adrenal gland using single-cell RNA sequencing. We reveal characteristic features of cell types within the human adrenal microenvironment and found immune activation of nonimmune cells in the adrenal endothelial cells. We also reveal that abundant immune cells occupied a lot of space in adrenal gland. Additionally, Sex-related diversity in the adrenocortical cells and different gene expression profiles between the left and right adrenal gland are also observed at single-cell resolution. Together, at single-cell resolution, the transcriptomic map presents a comprehensive view of the human adrenal gland, which serves as a fundamental baseline description of this organ and paves a way for the further studies of adrenal diseases.

Diagnostic accuracy of using multiple cytokines to predict aldosterone-producing adenoma

“…RANTES known to expressed and secreted by activated and normal T cell 23 , IP-10 attracting activated T, and CXCL9 involving in T cell migration 24,25 , were all showing the close relationship with T cells, and those cytokines were strongly associated with CD8 + T-cell infiltration in solid tumors [26][27][28] . Early researches have detected the abundant lymphocytic infiltration in adrenocortical tumor, and recent single cell sequencing studies have further detected the CD8 + T cells with highest proportion in normal adrenal glands 7,29,30 , therefore we speculated that these inflammatory factors might play a role in unilateral PA formation.…”

“…Notably, the elevating factors in the adrenal veins were macrophage and monocyte associated factors, including granulocyte colony stimulating factor (G-CSF), macrophage colony stimulating factor (M-CSF), macrophage-derived chemokine (MDC), monocyte chemokine protein-1 (MCP-1) 39 – 41 . In addition, other elevating cytokines such as FMS-like Tyrosine kinase 3 Ligand (FLT3L), IL-15 have also been identified as pro-inflammatory cytokines, mainly involved in the regulation of T cells, according to previous studies 42 , 43 ,and normal adrenal gland microenvironment also demonstrated the high portion of macrophage 7 , which implicating the important function conducted by both macrophage and CD8 + T cells.…”

“…Studies have shown that aldosterone can not only promote the secretion of inflammatory factors, like transforming growth factor-β (TGF-β), CTGF, CCL2, Smad2/3, and nuclear factor-kappaB (NF-kB) 3 – 5 , but also induce inflammatory responses in various organs and tissues, including kidney, cardiovascular system and artery vessels 6 . Furthermore, the existence of plentiful amounts of immune cells and active immune effects in the adrenal gland have been demonstrated by single-cell RNA sequencing (scRNA-seq) 7 , which implicated the pathogenic mechanism of adrenal tumors might be regulated by immune cells.…”

Models of Congenital Adrenal Hyperplasia for Gene Therapies Testing

“…scRNA-seq experiments allow the study of important intercellular variability and provide a clearer understanding of the influence of gene expression under more or less favorable conditions. Despite the fact that there are pioneering studies in which healthy adrenal glands have been examined on single samples using scRNA-seq of healthy adult adrenal glands [ 65 ], to our knowledge a detailed description of this tissue on a large sample dataset is not yet complete.…”

“…The analysis of the adult adrenal gland demonstrated that well-known cell types persist inside the organ, such as adrenal fasciculate, glomerulose, capsule cells, as well as immune, endothelial, stromal cells, and others. Defined cell clusters exhibited high correlation across humans and mice, excluding the chromaffin population, which demonstrated a difference between these two species, namely one chromaffin cell cluster in humans and two in mice [ 65 , 71 , 72 ]. In the study of chronic stress, the scRNA-seq approach promoted the findings that the hypertrophy of the zona fasciculata cells is responsible for organ growth; there is a new group of cells with increased expression of Abcb1b that respond to stress adaptation [ 72 ].…”