【文献速览】-Spatiotemporal analysis of human intestinal development at single-cell resolution

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.

人类肠道的发育还没有被很好地理解。在这里，我们将单细胞RNA测序和空间转录组学联系起来，以表征肠道形态发生的时间。我们鉴定了101种细胞状态，包括上皮细胞和间充质祖细胞群和与关键形态发生里程碑相关的程序。我们描述了隐窝-绒毛轴形成的原理;发育中的肠道的神经、血管、间充质形态发生和免疫群体。我们确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，并描述了它们的不同功能，包括作为血管生态位细胞。我们确定了Peyer s斑和肠道相关淋巴组织(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提出了一个无偏的分析形态梯度，直接连续波的细胞分化和定义细胞和位置联系到罕见的发育性肠道疾病。我们编制了一个公开的在线资源，时空分析资源的胎儿肠道发育(STAR-FINDer)，以促进进一步的工作。