Using a Monocle single-cell trajectory analysis, we uncovered a clear potential differentiation trajectory from “intestinal stem cell–like” cells (LGR5, CD44, EPHB2), through transit amplifying cells (OLFM4) and Paneth cells (DEFA5, DEFA6), to the dominant absorptive enterocyte clusters (APOA1, APOA4) enriched for putative SARS-CoV-2–susceptible cells (Supplemental Figure 4), suggesting that terminal differentiated cells are likely to be the most susceptible to infection. Here, DEFA6 is linked to infection.