Tapeworm stem cells as drivers of regeneration and reproduction

绦虫干细胞作为再生和繁殖的驱动力

• 批准号: 10366097
• 负责人: Tania Rozario
• 金额: $ 45.3万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-05 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10366097
• 关键词: Adult; Amputation; Animal Model; Anterior; Antibodies; Biological Assay; Biology; Cell Nucleus; Cell Separation; Cell Surface Receptors; Cell Transplantation; Cellular biology; Cessation of life; Cestoda; Cestode Infections; Competence; Complex; Comprehension; Cues; Cyst; Detection; Development; Disease; Distress; Economics; Feeling; Foundations; Fresh Water; Future; Gene Expression; Gene Expression Profiling; Genes; Genetic; Germ Cells; Goals; Growth; Hand; Head and neck structure; Helminths; Human; In Situ Hybridization; Injury; Intestines; Investigation; Label; Lethargies; Life Cycle Stages; Livestock; Longevity; Methodology; Modeling; Modernization; Molecular; Natural regeneration; Nature; Neck; Neoplasm Metastasis; Nervous system structure; Organ failure; Output; Parasites; Pathologic; Physiological; Physiology; Planarians; Platyhelminths; Play; Pluripotent Stem Cells; Prevention; RNA; RNA Interference; Rat tapeworm; Regulation; Reproduction; Research; Role; Seizures; Signal Transduction; Stains; Structure of primordial sex cell; Symptoms; System; Techniques; Testing; Thymidine; Transcript; Transplantation; Work; Zoonoses; analog; base; cell behavior; combat; design; drug development; fascinate; frontier; functional genomics; genetic approach; innovation; novel therapeutics; pathogen; pluripotency; regenerative; reproductive; screening; stem cell biology; stem cell population; stem cell self renewal; stem cells; stemness; tissue repair; tool; trait; transcriptomics; transmission process

Abstract Parasitic flatworms, such as tapeworms, have global reach and cause a wide variety of symptoms from intestinal distress and lethargy to organ failure, seizures, and even death. These parasites have complex life cycles and a remarkable capacity for growth, reproduction, regeneration, and longevity. These physiological traits are enabled by stem cells, thus understanding stem cell behaviors and regulation in these parasites has the capacity to uncover a broad range of potential targets that can be exploited for future drug development. My foundational work establishing the rat tapeworm, Hymenolepis diminuta, as a tractable modern model organism and my initial characterization of stem cells and regeneration in this system make it ideal for this study. My goal is to elucidate stem cell-driven regeneration and reproduction in this tapeworm. I seek to discover the signals that regulate stem cell potency and enable regeneration of tapeworm proglottids, which are each a functional reproductive unit. To this end, I will identify subpopulations of stem cells and functionally assay for pluripotent potential using innovative cell isolation and transplantation methodologies. I have previously shown that microenvironmental signals that regulate regenerative ability are anteriorly biased. Thus, I will undertake high- throughput gene expression screening and RNA interference by targeting factors that are polarized along the anterior-posterior axis across the regeneration-competent tapeworm neck. Furthermore, I will functionally identify genetic regulators of the germline lineage and investigate the potential plasticity of germ cells, as well as their coordination with mechanisms that govern proglottid regeneration. These innovative studies exploit the natural progression of parasite development to make genetic discoveries and take a stem cell-centric approach to illuminate parasite biology. This is significant as I will be able to make fundamental discoveries in both stem and germ cell biology, as well as in a greater disease-relevant context.

抽象的 寄生虫（例如tape虫）具有全球影响力，并引起各种症状 肠道苦难和嗜睡对器官衰竭，癫痫发作甚至死亡。这些寄生虫有复杂的生活 循环和显着的生长，再生产，再生和寿命的能力。这些生理 干细胞启用了特征，因此了解这些寄生虫中的干细胞行为和调节 发现可以利用的广泛潜在目标的能力，这些目标可以用于未来的药物开发。我的 建立大鼠tape虫的基础作品，hymenolepis diminuta，作为一种可拖动的现代模型有机体 我对干细胞的最初表征和该系统中的再生使其成为这项研究的理想选择。我的目标 是为了阐明这种tape虫中的干细胞驱动的再生和繁殖。我试图发现信号 调节干细胞效力和启用tapeemort proglottids的再生，它们都是功能性的 生殖单元。为此，我将确定干细胞的亚群并在功能上测定多能 使用创新的细胞分离和移植方法的潜力。我以前已经表明 调节再生能力的微环境信号是偏见的。因此，我将高度承担 吞吐基因表达筛选和RNA干扰沿极化的靶向因子 跨再生能力的tape虫颈部前后轴。此外，我将在功能上识别 种系谱系的遗传调节剂，并研究生殖细胞的潜在可塑性及其 与支配前后再生的机制的协调。这些创新的研究利用了自然 寄生虫发育的发展，以进行遗传发现并采用以干细胞为中心的方法 照明寄生虫生物学。这很重要，因为我将能够在STEM和 生殖细胞生物学以及与疾病相关的情况。