The b ⁰⁺ Amino Acid Transporter Defines a Selenium-utilization Enterocyte Program in the Human Intestine

Selenium is an essential trace element incorporated into selenoproteins as selenocysteine, yet the intestinal cellular programs associated with selenium utilization remain poorly defined. Here, we performed a large-scale single-cell transcriptomic analysis of 169,068 human enterocytes from 105 donors to systematically profile nine candidate selenium transporter systems and their relationship to selenoprotein expression. Among all transporters examined, the b ⁰⁺ amino acid transporter system (SLC3A1/SLC7A9) showed the strongest and most maturation-independent association with selenoproteins, including SELENOP (Spearman r = 0.489) and GPX4 (r = 0.392), with enrichment across 21 of 24 detected selenoproteins in b ⁰⁺ -complete versus transporter-negative enterocytes. These associations were robust across individual donors and confirmed by pseudobulk validation, and were only partially explained by enterocyte maturation state and intestinal segment after covariate adjustment, indicating both differentiation-dependent and differentiation-independent components. Furthermore, LRP1 and LRP5, not the canonical SELENOP receptors LRP2 and LRP8, emerged as the predominant LRP family members in enterocytes and were preferentially enriched in b ⁰⁺ -complete cells, suggesting a distinct intestinal SELENOP receptor landscape. These findings provide the first single-cell transcriptomic evidence that b ⁰⁺ transporter expression is associated with a selenoprotein-enriched enterocyte state and identify candidate receptor programs for intestinal SELENOP uptake.