瑞士巴塞尔大学J. Gray Camp等研究人员合作绘制出人类发育图谱。这一研究成果于2021年5月20日在线发表在国际学术期刊《细胞》上。

器官由器官发生过程中跨越瞬时状态的多种细胞类型组成。为了在人类发育过程中研究这种多样性，研究人员从呼吸道和胃肠道等多个发育中的内胚层器官中生成了一个单细胞转录组图谱。研究人员阐明了细胞状态、转录因子以及跨谱系的器官特异性上皮干细胞和间质相互作用。研究人员将这个图谱作为高维搜索空间，从而在多种培养条件下对人类多能干细胞（hPSC）衍生的肠道类器官（HIOs）进行基准测试。

结果表明，HIOs概括了参考细胞状态，并使用HIOs重构了肠上皮和间充质出现的分子动力学。研究人员发现，间充质衍生的微环境表明，NRG1增强了肠道干细胞的体外成熟，并且同源盒转录因子CDX2是人类上皮和间充质区域化所必需的。这项工作结合了细胞图谱和类器官技术，可用于了解人体器官的发育如何协调。

附：英文原文

Title: Charting human development using a multi-endodermal organ atlas and organoid models

Author: Qianhui Yu, Umut Kilik, Emily M. Holloway, Yu-Hwai Tsai, Christoph Harmel, Angeline Wu, Joshua H. Wu, Michael Czerwinski, Charlie J. Childs, Zhisong He, Meghan M. Capeling, Sha Huang, Ian A. Glass, Peter D.R. Higgins, Barbara Treutlein, Jason R. Spence, J. Gray Camp

Issue&Volume: 2021-05-20

Abstract: Organs are composed of diverse cell types that traverse transient states during organogenesis. To interrogate this diversity during human development, we generate a single-cell transcriptome atlas from multiple developing endodermal organs of the respiratory and gastrointestinal tract. We illuminate cell states, transcription factors, and organ-specific epithelial stem cell and mesenchyme interactions across lineages. We implement the atlas as a high-dimensional search space to benchmark human pluripotent stem cell (hPSC)-derived intestinal organoids (HIOs) under multiple culture conditions. We show that HIOs recapitulate reference cell states and use HIOs to reconstruct the molecular dynamics of intestinal epithelium and mesenchyme emergence. We show that the mesenchyme-derived niche cue NRG1 enhances intestinal stem cell maturation in vitro and that the homeobox transcription factor CDX2 is required for regionalization of intestinal epithelium and mesenchyme in humans. This work combines cell atlases and organoid technologies to understand how human organ development is orchestrated.

DOI: 10.1016/j.cell.2021.04.028

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00531-6