The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung’s disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease.

人类肠道的细胞景观在整个生命过程中都是动态的，在子宫内发育并根据功能需求和环境暴露而变化。在这里，为了全面绘制细胞谱系图谱，我们对来自发育中多达 5 个解剖区域以及健康儿童和成人肠道中多达 11 个不同解剖区域的近 50 万个细胞进行了单细胞 RNA 测序和抗原受体分析。这揭示了整个人类肠道中存在转录不同的 BEST4 上皮细胞。此外，我们将 IgG 传感视为肠簇细胞的功能。我们描述了发育中的肠神经系统中的神经细胞群，并预测了与先天性巨结肠相关的基因的细胞类型特异性表达。最后，利用系统方法，我们确定了在人类早期发育中驱动次级淋巴组织形成的关键细胞参与者。我们证明这些程序在炎症性肠病中被采用，以在炎症部位招募和保留免疫细胞。这个肠道细胞目录将为发育、稳态和疾病中的细胞程序提供新的见解。