Serosal Mesothelium and Vascularization of the Gut

描述（由申请方提供）：我们的数据显示，来自浆膜间皮（SM;心外膜（PE）/心外膜的肠道等效物）的细胞亚群经历上皮/间质转化（EMT）。这些细胞自由迁移以填充消化道的所有器官，并分化成包括肠壁血管生成细胞在内的多种细胞。因此，SM分化反映了PE发展的特定方面，但在其发展概况也存在显着差异。虽然SM在发育中具有广泛的作用，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，我们确定了分离的成年SM可以被诱导分化为平滑肌。这表明，成年SM保留血管生成潜力，并表明SM可能作为一个自然发生的祖细胞的来源，用于修复。我们的目标将探讨三个独立的，但互动的概念，有关的潜力SM的发展和修复。目的1将使用异位移植来确定SM和PE是否具有可互换或内在可变的潜力。目的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将使用基因标记的SM移植物来确定其在损伤后血管修复调节中的作用。总之，这些研究将确定SM的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。这些研究将形成未来分析发育和疾病中异常血管形成的背景。

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.