Serosal Mesothelium and Vascularization of the Gut

描述（由申请人提供）：我们的数据显示，浆膜间皮（SM；肠等效的心外膜(PE)/心外膜）细胞亚群经历上皮/间充质转化（EMT）。这些细胞可以自由地迁移到消化道的所有器官，并分化成各种各样的细胞，包括肠道的壁血管生成细胞。因此，SM分化反映了PE发展的特定方面，但它们的发展概况也存在显著差异。虽然SM在发育中具有广泛的作用是明确的，但其在血管形成和器官发生中的潜力和调节是完全未知的。此外，我们确定离体成年SM可以诱导分化为平滑肌。这表明成年SM保留了血管生成潜能，并提示SM可能作为修复祖细胞的自然来源。我们的目标是研究与SM在发育和修复中的潜力相关的三个独立但相互作用的概念。目的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电位。目的2将使用谱系和消融模型来确定SM如何调节肠道血管形态发生。Aim 3将使用基因标记的SM移植来确定其在损伤后血管修复调节中的作用。综上所述，这些研究将确定SM是如何调控血管发育和修复的。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血管的来源以及如何调节血管的形成模式。这些研究将为未来分析发育和疾病中血管形成异常奠定基础。

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.