Identification of a novel progenitor cell population for tissue homeostasis and regeneration of the Drosophila prostate

摘要： 果蝇附腺是哺乳动物前列腺的功能类似物。这个组织是 负责制造和分泌精液蛋白质和其他分子，这些蛋白质和其他分子对成功的生殖至关重要。 生殖研究表明，这种组织随着年龄的增长而生长， 通过经历称为内循环的变异细胞周期来促进这种生长。初步数据显示， 成人附腺含有一种新的有丝分裂祖细胞群， 组织稳态和损伤后的再生。该研究计划将建立必要的工具， 未来的研究和调查附腺祖细胞群体随年龄，交配， 并且在从损伤再生期间通过：（1）使用单细胞RNA测序来建立祖细胞 特异性转录组和祖细胞特异性驱动系，（2）表征细胞周期状态， 这些细胞的分化能力与年龄和交配，和（3）描述这些细胞的功能， 副腺的体内平衡和再生。这里提出的实验将允许额外的 单细胞RNA测序技术培训和谱系追踪和细胞周期分析培训 调节新的祖细胞群体。由于它的结构和功能相似， 哺乳动物前列腺和果蝇的短寿命，果蝇附腺是一个有效的模型 用于研究前列腺组织稳态失调、生育问题和再生。

Abstract: The Drosophila melanogaster accessory gland is a functional analog of the mammalian prostate. This tissue is responsible for making and secreting seminal fluid proteins and other molecules that are critical for successful reproduction. It has been shown that this tissue grows with age and the main, binucleated, epithelial cell type contributes to this growth by undergoing a variant cell cycle termed an endocycle. Preliminary data reveals that the adult accessory gland contains a novel, mitotic progenitor cell population that may also play a key role in tissue homeostasis and regeneration upon damage. This research plan will establish the tools necessary for future studies and investigate the dynamics of the accessory gland progenitor cell population with age, mating, and during regeneration from damage by: (1) using single cell RNA sequencing to establish a progenitor cell specific transcriptome and progenitor cell specific driver lines, (2) characterizing the cell cycle status and differentiation ability of these cells with age and mating, and (3) describing the function of these cells in accessory gland homeostasis and regeneration. The experiments proposed here will allow for additional technical training in single cell RNA sequencing and analytical training in lineage tracing and cell cycle regulation of a novel progenitor cell population. Due to it's structural and functional similarities to the mammalian prostate and the short lifespan of the fruit fly, the Drosophila accessory gland is an effective model for studying misregulation of prostate tissue homeostasis, fertility issues, and regeneration.