Mechanoregulation of Tissue Morphogenesis

描述（由申请人提供） 摘要：组织形态发生的机械调节摘要再生医学在治疗退行性疾病方面有很大的希望，通过刺激受损组织进行自我修复，或者在身体不能自我修复时用工程组织替代它们。因此，对组织再生中的调节机制和调节这些过程的能力的基本理解对于再生医学的最终成功至关重要。遗传变异或环境因素导致的调节过程偏差也是许多疾病的根本原因。然而，很少有人知道多祖系统如何解释的线索，在微环境中，如全球几何指导，局部细胞间的相互作用，和细胞外基质的性质，共同驱动的形态发生过程中形成的组织结构在多个长度尺度。我们最近的研究表明，新的机械调节计划利用肌原祖细胞在横纹肌的组织。本申请的目的是开发一种创新的细胞机械调节方法，该方法配备了一组新的技术模块，以阐明细胞自组织过程中复杂的调节机制。作为一个模型系统，多阶段的肌原性自组织过程，包括极化，对齐，融合，和肌祖细胞的肌原纤维形成将被用来破译肌发生过程中的细胞自组织的机械调节。该项目将解决长期存在的多细胞自组织生物学问题，这推动了组织形态发生的出现。该项目的成功完成将为阐明各种组织的再生过程建立机械调节方法，并将对未来的再生医学产生深远的影响。 公共卫生相关性：再生医学在治疗退行性疾病方面有很大的希望，它可以刺激受损组织进行自我修复，或者在身体无法自我修复时用工程组织替代它们。拟议的细胞机械调节研究将使我们能够了解在正常发育和疾病期间控制组织形成的基本过程，并最终导致再生医学的新方法。

DESCRIPTION (Provided by the applicant) Abstract: Mechanoregulation of Tissue Morphogenesis Abstract Regenerative medicine holds great promise in treating degenerative diseases by stimulating damaged tissues to repair themselves, or replacing them with engineered tissues when the body cannot heal itself. A fundamental understanding of the regulatory mechanisms in tissue regeneration and the ability to modulate these processes, therefore, are critical to the ultimate success of regenerative medicine. Deviations of the regulatory processes as a result of genetic variation or environmental factors also represent the underlying causes of many diseases. However, little is known about how multi-progenitor systems interpret the cues in the microenvironment, such as global geometric guidance, local cell-cell interactions, and extracellular matrix properties, to collectively drive the morphogenic process of fashioning tissue structures across multiple length scales. Our recent studies suggest novel mechanoregulation schemes utilized by myogenic progenitors in the organization of striated muscle. The objective of this application is to develop an innovative cell mechanoregulation approach equipped with a set of novel technological modularities to elucidate the complex regulatory mechanisms during cellular self-organization. As a model system, the multi-stage myogenic self-organization process involving polarization, alignment, fusion, and myofibrillogenesis of muscle progenitors will be used to decipher the mechanoregulation of cellular self-organization during myogenesis. The project will address the long-standing biological question of multi-cellular self- organization, which drives the emergence of tissue morphogenesis. Successful completion of the project will establish the mechanoregulation approach for elucidating the regeneration processes of various tissues and will have profound impact on regenerative medicine in the future. Public Health Relevance: Regenerative medicine holds great promise in treating degenerative diseases by stimulating damaged tissues to repair themselves, or replacing them with engineered tissues when the body cannot heal itself. The proposed cell mechanoregulation study will allow us to understand the basic processes that govern the formation of tissue during normal development and diseases, and will eventually lead to novel approaches in regenerative medicine.