supply of blood-circulating serotonin [23]. In contrast, only scattered information indicate that enterocytes, a non-endocrine cell variety, actually express a full range of molecules supporting the metabolism of L-DOPA, dopamine and/or trace amines. Clarifying this point is all the far more significant for at the least three reasons: (i) SARS-CoV2 was shown to acutely or chronically infect enterocytes in COVID-19 ErbB4/HER4 Species patients [246], (ii) ACE2 expressed by enterocytes exert mucosal immune functions that shape the composition of gut microbiota [27] and, potentially, the related repertoire of microbiota-derived neuromediators [28], and (iii) patients with inflammatory bowel disease (IBD) exhibit both an intestinal down-regulation of ACE2 [291] and an abnormally high propensity to create neuropsychiatric disorders [32,33]. Inside the present perform, we initial surveyed human expression atlases to extract outcomes around the mRNA and protein levels exhibited by DDC and selected genes on the dopamine/trace amines synthetic pathways in enterocytes. In a second step, we then performed gene co-expression analyses on a lately published set of RNA-seq information obtained from SARSCoV2-infected human intestinal organoids [34]. We discovered that DDC and essential genes from the dopamine/trace amines synthetic pathways are not only extremely expressed by enterocytes under typical LIMK1 Gene ID conditions but additionally co-regulate with ACE2 in SARS-CoV2-infected human intestinal organoids. two. Outcomes two.1. Expression Patterns of ACE2, DDC and Key Genes from the Dopamine/Trace Amines Synthetic Pathways in Enterocytes in the Human Tiny Intestine Assessment with the genomic consensus dataset of the Human Protein Atlas (HPA) (combining and integrating three massive and independent datasets, as described in Supplies and Techniques) showed that, among 61 human tissues and cell sorts, the compact intestine could be the human tissue exhibiting the highest expression levels for ACE2, SLC6A19, DDC, SLC7A9, MAOA and SULT1A2 (Table 1 and Supplementary Material S1). The human little intestine was also in the top-5 tissues exhibiting the highest expression levels for SLC3A1 (ranked N 2), CYP2D6 (ranked N 2), SULT1A1 (ranked N 5) and SULT1A3 (ranked N 3) (Table 1 and Supplementary Material S1), all genes involved in the metabolism of dopamine and/or trace amines. In contrast, tyrosine hydroxylase (TH) mRNA levels were beneath the detection threshold in the human small intestine. To obtain insights into the identity of cells exhibiting such a pattern of expression in the human small intestine, we then mined the so-far biggest single cell RNA-seq expression atlas currently readily available for human gut cells [35,36]. We observed that ACE2 was incorporated within the molecular signature of only two cell types and localizations: enterocytes on the tiny intestine and enteroendocrine cells of the tiny intestine (Table two).Int. J. Mol. Sci. 2021, 22,3 ofTable 1. Ranks of mRNA expression levels reported in the human small intestine for ACE2, SLC6A19 and key genes on the dopamine/trace amine metabolic pathways. Gene Symbol ACE2 SLC6A19 SLC7A9 SLC3A1 SLC3A2 SLC7A8 SLC16A10 DDC MAOA MAOB CYP2D6 SULT1A1 SULT1A2 SULT1A3 TH Rank Reported for the Smaller Intestine amongst 61 Human Tissues 1 1 1 two 20 30 13 1 1 14 two 5 1 three not detectedAmong 61 human tissues and cells for which mRNA expression values are compiled in the HPA consensus dataset, the modest intestine ranks in the top-5 from the localizations exhibiting the highest mRNA levels for ACE2, DDC and several important genes in the dopamine/trac
