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 寄生扁虫，例如绦虫，具有全球影响力，并引起多种症状： 肠道不适和昏睡导致器官衰竭、癫痫发作，甚至死亡。这些寄生虫有复杂的生活 循环和卓越的生长、繁殖、再生和长寿能力。这些生理 性状是由干细胞赋予的，因此了解这些寄生虫中的干细胞行为和调节已经 发现可用于未来药物开发的广泛潜在目标的能力。我的 将大鼠绦虫（Hymenolepis diminuta）建立为易于处理的现代模式生物的基础工作 我对该系统中干细胞和再生的初步表征使其成为本研究的理想选择。我的目标 目的是阐明这种绦虫中干细胞驱动的再生和繁殖。我寻求发现信号 调节干细胞效力并使绦虫节片再生，节片都是功能性的 生殖单位。为此，我将鉴定干细胞亚群并进行多能功能测定 使用创新的细胞分离和移植方法的潜力。我之前已经证明过 调节再生能力的微环境信号存在前向偏差。因此，我将承担高 通过沿极化方向极化的目标因子进行通量基因表达筛选和 RNA 干扰 前后轴穿过具有再生能力的绦虫颈部。此外，我将在功能上识别 生殖系谱系的遗传调节因子，并研究生殖细胞的潜在可塑性及其 与控制节片再生的机制协调。这些创新研究利用了自然 寄生虫发育的进展以进行遗传发现并采取以干细胞为中心的方法 阐明寄生虫生物学。这很重要，因为我将能够在干细胞和 生殖细胞生物学，以及更大的疾病相关背景。