Comparison of human and mouse fetal intestinal tissues reveals differential maturation timelines

Maturation of the intestinal epithelium is a necessary step for development of a fully functioning gastrointestinal tract. Studies of rodent gastrointestinal development and maturation have long been used to guide understanding of human intestinal maturation, in part because accessing human gestational stage intestinal tissues to perform equivalent human studies can be difficult. Notable differences have already been described in the timing of key stages in intestinal development between rodents and humans, but the conservation of intestinal maturation events between the two species is poorly understood. We hypothesized that species-related differences in intestinal development would alter the timing of key maturation events between human and mouse. We tested our hypothesis by performing a detailed comparison of hallmarks of intestinal maturation in human and mouse gestational intestine, including markers that describe the emergence of intestinal cell types, functionality and structural integrity. Our study demonstrates clear timing differences between maturation stages in mouse and human, with the majority of human maturation hallmarks acquired post-partum, in contrast to their gestational emergence in mouse. Our work suggests caution when translating murine intestinal maturation observations to the human, and provides a maturation road map that will be helpful to those seeking to produce mature intestine from in vitro stem cell sources.