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

合作研究：通过激活骨形态发生蛋白信号传导对羊膜模式进行机械调节

• 批准号: 2325361
• 负责人: Jianping Fu
• 金额: $ 3.29万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-10-01 至 2026-09-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2325361&HistoricalAwards=false
• 关键词: Collaborative; Research; Mechanoregulation; Amnion; Patterning

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 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.

该项目旨在支持使用干细胞衍生的人类发展模型研究羊膜开发的基本研究。作为胎儿膜的最内向层，羊膜在介导营养转运和产生各种对维持妊娠重要的细胞因子方面起着至关重要的作用。该项目产生的见解将促进我们在早期人类发展方面的知识。该方法将有助于进行三维干细胞培养系统，用于疾病建模，细胞替代疗法和生殖医学。这项研究将促进基本科学的进步并提高孕产妇健康。外展和教育活动包括高中和本科课程发展，这将通过提供动手研究机会，丰富的研讨会和指导计划来实现。特别强调将扩大代表性不足的群体在研究活动中的参与。该项目的目标旨在应对理解早期人类发展期间羊膜发展的机械生物学的重大挑战。这项工作将是引导具有可调生物力学环境的干细胞衍生多细胞组织形成的尝试。该项目的成功完成将为三维人类多能干细胞培养提供新的创新平台。研究的定量形态和基因表达表征将提供有价值的知识，以更好地了解机械提示如何控制羊膜模式和人类胚胎囊的形成以及此过程中涉及的形态和基因表达动力学。该方法对于表征类似于人类胚胎（胚胎）和器官（Organoid）的复杂干细胞衍生的组织的发展而高度有价值。该项目中研究的机械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节如何调节羊膜的发展，并将为我们对新兴的自组织原理和发展机制的理解奠定重要的基础。这是通过评估的构成构成的依据，这些奖项反映了NSF的法规范围，并反映了构成构成的构成群体的构成。