Cells of the human intestinal tract mapped across space and time.
Cells of the human intestinal tract mapped across space and time.
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DOI：
10.1038/s41586-021-03852-1
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发表时间：
2021-09
期刊：
影响因子：
64.8
通讯作者：
Teichmann SA
中科院分区：
文献类型：
--
作者：
Elmentaite R;Kumasaka N;Roberts K;Fleming A;Dann E;King HW;Kleshchevnikov V;Dabrowska M;Pritchard S;Bolt L;Vieira SF;Mamanova L;Huang N;Perrone F;Goh Kai'En I;Lisgo SN;Katan M;Leonard S;Oliver TRW;Hook CE;Nayak K;Campos LS;Domínguez Conde C;Stephenson E;Engelbert J;Botting RA;Polanski K;van Dongen S;Patel M;Morgan MD;Marioni JC;Bayraktar OA;Meyer KB;He X;Barker RA;Uhlig HH;Mahbubani KT;Saeb-Parsy K;Zilbauer M;Clatworthy MR;Haniffa M;James KR;Teichmann SA
人体肠道的细胞景观在整个生命过程中是动态的，在子宫内发育，并根据功能要求和环境暴露而变化。在这里，为了全面绘制细胞谱系，我们使用单细胞RNA测序和抗原受体分析了来自发育中多达5个解剖区域和健康儿科和成人肠道中多达11个不同解剖区域的近50万个细胞。这揭示了在整个人类肠道中存在转录上不同的BEST 4上皮细胞。此外，我们牵连IgG传感作为肠簇细胞的功能。我们描述了肠神经系统发育中的神经细胞群，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，使用系统方法，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。我们表明，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。在沿着肠道的沿着不同位置分析来自胚胎、胎儿、儿科和成人肠组织的细胞，以构建发育中和成人肠道的单细胞图谱，包括所有细胞谱系。
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. Cells from embryonic, fetal, paediatric and adult human intestinal tissue are analysed at different locations along the intestinal tract to construct a single-cell atlas of the developing and adult human intestinal tract, encompassing all cell lineages.