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

果蝇前列腺组织稳态和再生的新型祖细胞群的鉴定

基本信息

批准号：
10219815
负责人：
Allison Box
金额：
$ 3.83万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10219815
关键词：
Ablation Adult Age Aging Animals Antigen-Presenting Cells Cell Cycle Cell Cycle Regulation Cell Differentiation process Cell division Cell physiology Cells Collection Data Diploid Cells Drosophila genus Drosophila melanogaster Epithelial Cells Fertility Future Gene Expression Gland Goals Growth Homeostasis Human Label Location Longevity Mitosis Mitotic Mitotic Cell Cycle Modeling Muscle Natural regeneration Neurons Organ Organism Partner in relationship Play Population Population Heterogeneity Prostate Proteins Recovery Regulation Reproduction Research Role Seminal fluid Structure Study models Techniques Tissues Training Urologic Diseases Variant Work analog cell population study cell type experimental study genetic manipulation male fertility novel organ regeneration progenitor response single-cell RNA sequencing sperm cell stem cells tissue regeneration tool transcriptome

项目摘要

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.

抽象的：果蝇附属腺是哺乳动物前列腺的功能类似物。该组织是负责制造和分泌精液蛋白质和其他对成功至关重要的分子生殖。研究表明，这种组织随着年龄的增长而生长，主要的双核上皮细胞类型通过经历称为内周期的变异细胞周期来促进这种生长。初步数据显示成体附属腺含有一种新型的有丝分裂祖细胞群，它也可能在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副腺祖细胞群随年龄、交配、以及在损伤再生过程中： (1) 使用单细胞 RNA 测序建立祖细胞特定转录组和祖细胞特定驱动系，(2) 表征细胞周期状态和这些细胞随着年龄和交配的分化能力，以及（3）描述这些细胞在辅助腺体内平衡和再生。这里提出的实验将允许额外的单细胞RNA测序技术培训以及谱系追踪和细胞周期分析培训新型祖细胞群的调节。由于其结构和功能与哺乳动物前列腺和果蝇寿命短，果蝇副腺是一个有效的模型用于研究前列腺组织稳态的失调、生育问题和再生。