Study of the selection process of spermatogenic stem cells using genetic barcoding

Research Project

Project/Area Number	17H07335
Research Category	Grant-in-Aid for Research Activity Start-up
Allocation Type	Single-year Grants
Research Field	Integrative animal science
Research Institution	National Institute for Basic Biology
Principal Investigator	Ikeda Tatsuro 基礎生物学研究所, 生殖細胞研究部門, NIBBリサーチフェロー (60803963)
Research Collaborator	YOSHIDA Shosei
Project Period (FY)	2017-08-25 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	マウス / 発生 / 細胞系譜 / 始原生殖細胞 / 精子幹細胞 / バーコーディング / Polylox
Outline of Final Research Achievements	During mouse embryonic development, about 40 primordial germ cells (PGCs) are first induced, and they proliferate to around 20 thousands before birth. Previous studies have suggested that in male mice only a subset of these PGCs generate spermatogenic stem cells (SSCs) which support lifelong spermatogenesis. However, the property of PGCs that contribute to SSCs remains unknown. We constructed an experimental system to introduce unique DNA sequence into each PGC, enabling lineage tracing of the developing germ cells at single-cell resolution. By using this system, we will be able to see the dynamic change of germ cell lineage, thus quantitatively reveal the selection timing/ratio of PGCs, and uncover the key feature of selected cells which can produce the next generation.
Academic Significance and Societal Importance of the Research Achievements	本研究では遺伝子バーコーディング法を適用し、胎児の生殖細胞から成体の幹細胞が選ばれるまでの「系図」を解析する実験系を構築した。今後この実験系を活用することで幹細胞の選択のメカニズムを明らかにできるに違いない。生殖細胞は配偶子（卵や精子）を作り受精によって次世代の子を生み出す唯一の細胞であり、品質の良い配偶子を作ることは生物が繁栄するために不可欠である。本研究を土台に生殖細胞を選択する仕組みが解明されたならば、生物が配偶子を品質管理する仕組みの理解や、培養によって配偶子を人工的に作る技術の発展に貢献すると期待される。