Physicochemical control of multilineage emergence

项目摘要 人类诱导多能干细胞(IPSCs)的独特之处在于它们保留了无限期自我更新的能力 同时保持自我组织和分化为胚胎和胚胎外的能力 血统。IPSCs已成为研究人类发育和疾病的强大工具，并已 与组织工程方法相结合，用于再生医学应用。兑现诺言，兑现诺言 IPSC的临床应用，进一步研究干细胞生态位在IPSC形态发生、谱系形成中的作用 规范，并需要功能成熟。虽然有机类方法彻底改变了我们的能力 模拟培养皿中器官水平的功能，它们通常由来自单一生殖层的细胞组成，缺少关键的 周围种群共有的线索，包括微血管和基质。此外，有机化合物是 在定义不明确的矩阵中生成，如Matrigel，它存在批次之间的差异，并且有限 可调性。为此，我们建议使用微图案化诱导原肠形成模型来更好地理解 旁分泌和机械线索引导原始干细胞的命运。此外，通过利用装配式技术， 模拟合成细胞外基质和动态微流控培养，我们的目标是更好地了解多个细菌 组织规范过程中的层交互作用。最后，我们提出可以使用改进的IPSC衍生品 以更好地了解患者在代谢紊乱方面的具体差异。总而言之，我们建议使用 综合方法将使IPSCs成为研究发育生物学和疾病的强大试验台 流程。

Project Summary Human induced pluripotent stem cells (iPSCs) are unique in that they retain their ability to indefinitely self-renew while maintaining the capacity to self-organize and differentiate into both embryonic and extraembryonic lineages. iPSCs have emerged as a powerful tool to study human development, and disease, and have been integrated with tissue engineering approaches for regenerative medicine applications. To fulfill the promise of iPSC clinical utility, further investigation of the role of the stem cell niche in iPSC morphogenesis, lineage specification, and functional maturation is needed. While organoid approaches have revolutionized our ability to mimic organ-level function in a dish, they typically are comprised of cells from a single germ layer, missing critical cues shared by surrounding populations including the microvasculature and stroma. In addition, organoids are generated in ill-defined matrices such as Matrigel, which suffers from batch-to-batch variation, and limited tunability. To this end, we propose using micropatterned induced gastrulation models to better understand how paracrine and mechanical cues guide primitive stem cell fate. In addition, by leveraging assembloid technologies, synthetic extracellular matrix mimics, and dynamic microfluidic culture, we aim to better understand multi-germ layer interactions during tissue specification. Finally, we propose that improved iPSC derivatives can be used to better understand patient-specific differences in metabolic disorders. Collectively, we propose that using an integrative approach will permit iPSCs to be a powerful testbed for studying developmental biology and disease processes.