Human‐like adrenal features in Chinese tree shrew revealed by multi-omics analysis of adrenal cell populations and steroid synthesis

The Chinese tree shrew has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce the steroid hormones and whether its production is regulated in the same way in the human and tree shrews. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, Macaca fascicularis, and mice. Tree shrew adrenal glands were found to express many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. We confirmed through biochemical analysis that tree shrew adrenal glands produce aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate. We were able to correlate genes in adrenal cell types in tree shrew with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Our work suggests that the adrenal glands of Chinese tree shrews may be closely related cell populations and functionally similar to the human adrenal gland. Our comprehensive results, which are publicly available at https://treeshrewdb.streamlit.app, should help guide the development of this animal model of adrenal gland disorders.