A key aspect of nutrient absorption is the exquisite division of labour across the length of the small intestine, with individual nutrients taken up at different proximal:distal positions. For millennia, the small intestine was thought to comprise three segments with indefinite borders: the duodenum, jejunum and ileum. By examining the fine-scale longitudinal transcriptional patterns that span the mouse and human small intestine, we instead identified five domains of nutrient absorption that mount distinct responses to dietary changes, and three regional stem cell populations. Molecular domain identity can be detected with machine learning, which provides a systematic method to computationally identify intestinal domains in mice. We generated a predictive model of transcriptional control of domain identity and validated the roles of Ppar-δ and Cdx1 in patterning lipid metabolism-associated genes. These findings represent a foundational framework for the zonation of absorption across the mammalian small intestine.

营养吸收的一个关键方面是小肠长度上的精细分工，各个营养物质在不同的近端和远端位置被吸收。几千年来，小肠被认为由三个边界不确定的部分组成：十二指肠、空肠和回肠。通过检查跨越小鼠和人类小肠的精细纵向转录模式，我们确定了对饮食变化产生不同反应的五个营养吸收领域，以及三个区域干细胞群。分子域的身份可以通过机器学习来检测，这提供了一种通过计算识别小鼠肠道域的系统方法。我们生成了域身份转录控制的预测模型，并验证了Ppar-δ和Cdx1在脂质代谢相关基因模式中的作用。这些发现代表了哺乳动物小肠吸收分区的基本框架。