2023-06-27 カリフォルニア工科大学(Caltech)
◆研究チームは、このモデルを通じて遺伝子の機能をテストすることができるため、発生過程における特定の要因の役割を理解することができます。また、マウスの胚様モデルと比べると、この人間のモデルはまだ進化の初期段階ですが、胎盤や卵黄嚢などの胚と外胚葉組織を含んでいます。これにより、人間の胚の発生過程における重要な相互作用を研究することができます。
◆研究者らは、このモデルが自然な発生過程に近い挙動を示すため、人間の子宮内での出来事をより正確に再現していると述べています。
<関連情報>
- https://www.caltech.edu/about/news/scientists-create-embryo-like-model-that-mimics-post-implantation-stage-of-human-development
- https://www.nature.com/articles/s41586-023-06368-y
多能性幹細胞由来の着床後ヒト胚モデル A model of the post-implantation human embryo derived from pluripotent stem cells
Bailey A. T. Weatherbee,Carlos W. Gantner,Lisa K. Iwamoto-Stohl,Riza M. Daza,Nobuhiko Hamazaki,Jay Shendure & Magdalena Zernicka-Goetz
Nature Published:27 June 2023
DOI:https://doi.org/10.1038/s41586-023-06368-y
We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.
Abstract
The human embryo undergoes morphogenetic transformations following implantation into the uterus, yet our knowledge of this crucial stage is limited by the inability to observe the embryo in vivo. Stem cell-derived models of the embryo are important tools to interrogate developmental events and tissue-tissue crosstalk during these stages1. Here, we establish a model of the human post-implantation embryo, a human embryoid, comprised of embryonic and extraembryonic tissues. We combine two types of extraembryonic-like cells generated by transcription factor overexpression with wildtype embryonic stem cells and promote their self-organization into structures that mimic several aspects of the post-implantation human embryo. These self-organized aggregates contain a pluripotent epiblast-like domain surrounded by extraembryonic-like tissues. Our functional studies demonstrate that the epiblast-like domain robustly differentiates to amnion, extraembryonic mesenchyme, and primordial germ cell-like cells in response to BMP cues. In addition, we identify an inhibitory role for SOX17 in the specification of anterior hypoblast-like cells2. Modulation of the subpopulations in the hypoblast-like compartment demonstrated that extraembryonic-like cells impact epiblast-like domain differentiation, highlighting functional tissue-tissue crosstalk. In conclusion, we present a modular, tractable, integrated3 model of the human embryo that will allow us to probe key questions of human post-implantation development, a critical window when significant numbers of pregnancies fail.
