Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK; Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford OX3 9DU, UK; Academic Paediatric Surgery Unit (APSU), Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 9DU, UK.
Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK; MRC WIMM Centre For Computational Biology, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
Cell. 2021 Feb 4;184(3):810-826.e23. doi: 10.1016/j.cell.2020.12.016. Epub 2021 Jan 5.
Development of the human intestine is not well understood. Here, we link single-cell RNA sequencing and spatial transcriptomics to characterize intestinal morphogenesis through time. We identify 101 cell states including epithelial and mesenchymal progenitor populations and programs linked to key morphogenetic milestones. We describe principles of crypt-villus axis formation; neural, vascular, mesenchymal morphogenesis, and immune population of the developing gut. We identify the differentiation hierarchies of developing fibroblast and myofibroblast subtypes and describe diverse functions for these including as vascular niche cells. We pinpoint the origins of Peyer's patches and gut-associated lymphoid tissue (GALT) and describe location-specific immune programs. We use our resource to present an unbiased analysis of morphogen gradients that direct sequential waves of cellular differentiation and define cells and locations linked to rare developmental intestinal disorders. We compile a publicly available online resource, spatio-temporal analysis resource of fetal intestinal development (STAR-FINDer), to facilitate further work.
人类肠道的发育过程还不甚清楚。在这里，我们结合单细胞 RNA 测序和空间转录组学，通过时间来描述肠道形态发生。我们鉴定出 101 种细胞状态，包括上皮和间充质祖细胞群，以及与关键形态发生里程碑相关的程序。我们描述了隐窝-绒毛轴形成的原则；神经、血管、间充质形态发生，以及正在发育的肠道中的免疫群体。我们鉴定了发育中的成纤维细胞和肌成纤维细胞亚型的分化层次，并描述了这些细胞的不同功能，包括作为血管壁龛细胞。我们确定了派尔集合淋巴结和肠相关淋巴组织 (GALT) 的起源，并描述了位置特异性免疫程序。我们利用我们的资源对指导细胞分化的顺序波的形态发生梯度进行了无偏分析，并确定了与罕见的发育性肠道疾病相关的细胞和位置。我们编制了一个公开可用的在线资源，即胎儿肠道发育的时空分析资源 (STAR-FINDer)，以促进进一步的工作。
