Serosal Mesothelium and Vascularization of the Gut

描述（由申请人提供）：我们的数据显示，来自浆膜间皮（SM；相当于心外膜（PE）/心外膜的肠道）的细胞子集经历上皮/间质转化（EMT）。这些细胞自由迁移，填充消化道的所有器官，并分化成多种细胞，包括肠道壁血管生成细胞。因此，SM 分化反映了 PE 发育的特定方面，但它们的发育概况也存在显着差异。虽然 SM 在发育中具有广泛的作用是显而易见的，但其在血管形成和器官发生中的潜力和调节却完全未知。此外，我们确定分离的成年 SM 可以被诱导分化为平滑肌。这表明成体 SM 保留了血管生成潜力，并表明 SM 可以作为修复祖细胞的天然来源。我们的目标将研究与 SM 在开发和修复方面的潜力相关的三个独立但互动的概念。目标 1 将使用异位嫁接来确定 SM 和 PE 是否具有可互换或固有可变的潜力。目标 2 将使用谱系和消融模型来确定 SM 如何调节肠道中的血管形态发生。目标 3 将使用带有基因标记的 SM 移植来确定其在调节损伤后血管修复中的作用。总而言之，这些研究将确定 SM 广泛但仍知之甚少的潜力如何调节血管发育和修复。公共卫生相关性：肠道主要血管的发育尚不清楚。我们的研究将确定胚胎肠道中血管的来源以及如何调节形成模式。这些研究将为未来分析发育和疾病中异常血管形成奠定基础。

DESCRIPTION (provided by applicant): Our data show that a subset of cells from the serosal mesothelium (SM; the gut equivalent of the proepicardium (PE)/epicardium) undergoes an epithelial/mesenchymal transition (EMT). These cells freely migrate to populate all organs of the alimentary canal and differentiate into a diverse set of cells including mural vasculogenic cells of the gut. Thus, SM differentiation mirrors specific aspects of PE development but significant differences in their developmental profiles also exist. While it is clear that SM has broad roles in development, its potential in and regulation of blood vessel formation and organogenesis is completely unknown. Additionally, we determined that isolated adult SM can be induced to differentiate into smooth muscle. This demonstrates that adult SM retains vasculogenic potential and suggests that the SM may serve as a naturally occurring source of progenitor cells for repair. Our aims will examine three independent yet interactive concepts related to the potential of SM in development and repair. Aim 1 will use heterotopic grafting to determine if SM and PE have interchangeable or inherently variable potential. Aim 2 will use lineage and ablation models to determine how SM regulates blood vessel morphogenesis in the gut. Aim 3 will use genetically-tagged SM transplants to determine its role in regulation of blood vessel repair after injury. Taken together these studies will determine how the broad yet still poorly understood potential of SM regulates vessel development and repair. PUBLIC HEALTH RELEVANCE: Development of the major blood vessels of the gut is not understood. Our studies will determine the source of blood vessels in the embryonic gut and how the pattern of formation is regulated. These studies will form the background for future analysis of abnormal blood vessel formation in development and disease.