Collaborative Research: Mechanoregulation of Amnion Patterning through Activation of Bone Morphogenetic Protein Signaling

该项目旨在支持利用干细胞衍生的人类发育模型研究羊膜发育的基础研究。羊膜作为胎膜的最内层，在介导营养物质运输和产生多种维持妊娠的重要细胞因子方面起着至关重要的作用。这个项目产生的见解将推进我们对早期人类发展的认识。这些方法将有助于合理设计用于疾病建模、细胞替代疗法和生殖医学的三维干细胞培养系统。这项研究将促进基础科学的进步，促进孕产妇保健。拓展和教育活动包括高中和本科课程开发，这将通过提供实践研究机会、丰富讲习班和指导计划来实现。将特别强调扩大代表性不足的群体参与研究活动。该项目的目标是解决在理解人类早期发育过程中控制羊膜发育的机械生物学方面的重大挑战。这项工作将是指导可调节生物力学环境下干细胞衍生的多细胞组织形成的第一次尝试。该项目的成功完成将为三维人类多能干细胞培养带来新的创新平台。研究的定量形态学和基因表达特征将为更好地理解机械线索如何控制羊膜图案和人类胚胎囊的形成，以及这一过程中涉及的形态学和基因表达动力学提供有价值的知识。这些方法对于描述类似人类胚胎（类胚胎）和一般器官（类器官）的复杂干细胞衍生组织的发育具有很高的价值。本项目的机制研究将阐明骨形态发生蛋白信号通路及其与机械信号的交叉调控是如何调控羊膜发育的，为进一步了解羊膜的自组织原理和发育机制奠定重要基础。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project is to support the fundamental research to study amnion development using a stem cell-derived human development model. As the innermost layer of the fetal membrane, amnion plays a crucial role in mediating nutrient transportation and producing a variety of cytokines that are important for maintaining pregnancy. The insights generated by this project will advance our knowledge in early human development. The methods will assist in the rational design of three-dimensional stem cell culture systems for disease modeling, cell replacement therapy, and reproductive medicine. This research will promote the progress of fundamental science and advance maternal health. Outreach and educational activities include high school and undergraduate curriculum development, which will be achieved by offering hands-on research opportunities, enrichment workshops, and mentoring program. Special emphasis will be placed on broadening participation of underrepresented groups in the researched activities. The objective of this project is set to address the significant challenge in understanding the mechanobiology governing amnion development during early human development. This work will be the first attempt to guide the formation of stem cell-derived multicellular tissues with tunable biomechanical environments. Successful completion of the project will lead to new innovative platforms for three-dimensional human pluripotent stem cell culture. The researched quantitative morphological and gene expression characterizations will provide valuable knowledge towards a better understanding on how mechanical cues control amnion patterning and the formation of the human embryonic sac, and the morphological and gene expression dynamics involved in this process. The methodologies will be highly valuable for characterizing the development of complex stem cell-derived tissues that resemble human embryos (embryoid) and organs (organoid) in general. Mechanistic investigations researched in this project will elucidate how the bone morphogenetic protein signaling pathway and its cross-regulations with mechanical signals regulate amnion development, and will lay important foundations for advancing our understanding of the emergent self-organizing principles and developmental mechanisms.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.