The Study and Manipulation of Male Germline Stem Cells

雄性生殖干细胞的研究和操作

• 批准号: RGPIN-2019-07124
• 负责人: Honaramooz, Ali
• 金额: $ 2.04万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=716396
• 关键词: Study; Manipulation; Male; Germline; Stem

The testis is a prolific and efficient organ that produces hundreds of millions of sperm per day throughout the adult life. The foundation of this process is a very small group of cells known as male germline stem cells (MGSC). These stem cells have great potential because they are the only adult stem cells that can contribute genes to the next generation, thereby holding the key to male fertility. Manipulation of these stem cells can even lead to their differentiation into cells of other tissues (e.g., cardiac muscle or insulin-producing cells), raising hope that they can be used as an alternative source of adult stem cells for regenerative therapies. However, our knowledge of MGSC is limited because important questions regarding their unique characteristics and stem cell multipotency remain unanswered. The long-term objective of my research program is to uncover the fundamental aspects of MGSC biology and to harness their potential for the benefit of animal and human reproduction in Canada and beyond. Using neonatal pig testis tissue and cells as a model, we have made pioneering discoveries toward our long-term objectives. For instance, we have shown that when pig testis cells are injected under the back skin of mice they can regenerate functional testis tissue that is morphologically and functionally identical to intact testis tissue. These results support the use of this novel model to examine the factors required for normal formation of the testis or to test the potential effect of environmental toxicants on testis formation. Images of our recent results were among the top 20 selected nationwide by NSERC Science Exposed 2017 and 2018. NSERC-DG funding will enable the continuation of my research program on the biology and application of MGSC by: 1) examining testis tissue regeneration following incorporation into 3-dimensional printed tissue scaffolds and manipulation of hormones and growth factors thought to be involved in cell migration and tissue formation/regeneration; 2) examining cultured MGSC to explore their unique genes and biomarkers and stem cell multi-potency; and 3) investigating the culture conditions leading to exponential proliferation of MGSC for use in downstream applications, as well as for induction of spermatogenesis in vitro. This is a novel and exciting research area with tremendous potential applications, including improvement of reproductive efficiency in livestock, manipulation of MGSC for use as a novel approach for producing genetically-modified (transgenic) farm animals, conservation of genetic material of endangered or prized animals, and potential use in restoring fertility of prepubertal boys undergoing cancer treatments. This research will train 2 PhD, 2 MSc, and 5 summer undergraduate students, who upon completion will be well positioned to pursue further studies or careers in veterinary medicine or reproductive biology.

睾丸是一个多产而高效的器官，在成年人的一生中，每天都会产生数亿个精子。这个过程的基础是一组非常小的细胞，被称为男性生殖系干细胞（MGSC）。这些干细胞具有巨大的潜力，因为它们是唯一能够向下一代提供基因的成体干细胞，因此掌握着男性生育能力的关键。对这些干细胞的操作甚至可以导致它们分化成其他组织的细胞（例如，心肌或产生胰岛素的细胞），这增加了它们可以用作再生治疗成体干细胞的替代来源的希望。然而，我们对MGSC的了解是有限的，因为关于它们独特的特性和干细胞多能性的重要问题仍然没有答案。