Fig. 1: Anatomy of human and mouse adrenal gland (AG) revealed from single nuclei/cell analysis.

a 1536 single nuclei of human AG from three different patients were sequenced with Smart-seq2 to an average depth of 485,000 reads per cell. Cells with high-quality (n = 1322) were selected and further processed with PAGODA. Cells were grouped into ten different clusters, including cortex (in brown and gray colors), chromaffin (blue hC4), mesenchymal (purple hC7), endothelial (light blue hC6), and immune cells (i.e., T cells hC10 and macrophages hC2 in green colors). b 1920 single cell of mouse AG from five different samples were sequenced with Smart-seq2 to an average depth of 670,000 reads per cell. Cells with high-quality (n = 1763) were selected and further processed with PAGODA. Cells were grouped into nineteen different clusters, including cortex (in brown and gray colors), chromaffin (blue mC15 and light blue mC11), mesenchymal (red mC6), capsule (purple mC13), endothelial (light blue mC2 and mC4), glial (orange mC10), and immune cells (i.e., T cells mC17 and mC18, and macrophages mC3, mC8, and mC14 in green colors). Human and mouse adrenal glands zonation⁴⁹ is illustrated in (c). c, d A comparison of the specific gene signature between human and mouse revealed similar transcription signatures for mesenchymal, endothelial, and immune clusters, nevertheless, the two different postnatal chromaffin cells could only be differentiated in mouse. d Hierarchical clustering of cells and expression of a panel of markers including noradrenergic (NOR), mesenchymal (MES), endothelial (Endot.), and migratory (Migrat.). e–g A population of cells with a significant high expression of progenitor markers (i.e., SOX6, ERBB3, RTTN, FDR<0.01) and high differentiation potential found uniquely in human AG, is sourcing the chromaffin cells as indicated by velocity, entropy, and pseudotime analyses. h In this process, gene expression elapses from an undifferentiated stem-like- (i.e., RTTN+) to an adrenergic signature (PNMT+), passing by a noradrenergic stage (i.e., DBH+), as indicated by the pseudotime of the underlying cellular process. Results in (c), (e), and the top inserts in (d) and (h) represent cell clusters by color in (a).