Role of ngn3, a bHLH transcription factor, in the establishment and maintenance of the mouse spermatogenic stem cells

bHLH转录因子ngn3在小鼠生精干细胞建立和维持中的作用

• 批准号: 17570177
• 负责人: YOSHIDA Shosei
• 金额: $ 2.24万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17570177/
• 关键词: germ cells; mouse; spermatogenesis; stem cells; ngn3; cell differentiation; self-renewal; spermatogonia

The aim of this study was to investigate the establishment of the spermatogenic stem cells, their behaviors in the mature testes, and the underlying molecular mechanisms. This has been done taking advantages of our previous identification of ngn3 (neurogenin3, a basic-helix-loop-helix transcription factor), which is expressed in undifferentiated spermatogonia, a tiny spermatogonial population that harbors the stem cell function.Emergence of the ngn3+ undifferentiated spermatogonia was investigated during the pre-pubertal and pubertal periods and it has been revealed that the very first round of spermatogenesis lacks the ngn3+ undifferentiated spermatogonia stage, while the following waves and spermatogenesis found in matured testes were all derived from the ngn3-positive undifferentiated spermatogonia. This indicates that the stem cell stage may not be indispensable for the spermatogenic differentiation process and provides an intriguing notion widely for the stem cell study. In addition, it is suggested that some of the Ngn3+ spermatogonia play very important roles for the occasional loss of actually self-renewing stem cells and replenish the stem cell pool, which is important for the long-term robustness of the spermatogenesis.These results would provide basic findings valuable for the strategy against upcoming human problems such as male infertility or overpopulation.

本研究的目的是探讨生精干细胞的建立、在睾丸中的行为及其分子机制。这是利用我们以前对ngn 3的鉴定来完成的。（神经生成素3，一种碱性螺旋环螺旋转录因子），其在未分化的精原细胞中表达，一个微小的精原细胞群体，具有干细胞功能。ngn 3+未分化精原细胞的出现在预处理过程中进行了研究。青春期和青春期，并且已经揭示了精子发生的第一轮缺乏NGN 3+未分化的精原细胞阶段，而成熟睾丸中的后续波和精子发生均来源于ngn 3阳性的未分化精原细胞。这表明，干细胞阶段可能不是生精分化过程中必不可少的，并提供了一个有趣的概念，广泛的干细胞的研究。此外，部分Ngn 3+精原细胞在实际自我更新的干细胞的偶尔丢失和补充干细胞库中发挥着非常重要的作用，这对精子发生的长期稳健性至关重要，这些结果将为应对即将到来的人类问题如男性不育或人口过剩提供有价值的基础研究结果。

项目成果

The first round of mouse spermatogenesis is a distinctive program that lacks the self-renewing spermatogonia stage

• DOI: 10.1242/dev.02316
• 发表时间: 2006-04-15
• 期刊: DEVELOPMENT
• 影响因子: 4.6
• 作者: Yoshida, S;Sukeno, M;Nabeshima, Y
• 通讯作者: Nabeshima, Y

CTX family cell adhesion molecule, JAM4, expresses in stem cell- and progenitor cell populations of both male germ cell and hematopoietic cell lineages.

CTX 家族细胞粘附分子 JAM4 在雄性生殖细胞和造血细胞谱系的干细胞和祖细胞群中表达。

• 发表时间: 2006
• 期刊: Mol. Cell. Biol. 24巻
• 作者: Nagamatsu G;Ohmura M;Mizukami T;Hamaguchi I;Hirabayashi S;Yoshida S;Hata Y;Suda T;Ohbo K.
• 通讯作者: Ohbo K.

生殖幹細胞ニッチー「モデル生物」から「ほ乳類」を考える

从生殖干细胞生态位“模式生物”的角度思考“哺乳动物”

• 发表时间: 2007
• 期刊: 医学のあゆみ 221
• 作者: M.Kanatsu-Shinohara;K.Inoue;N.Ogonuki;H.Miki;S.Yoshida;S.Toyokuni;J.Lee;A.Ogura;T.Sinohara;吉田松生
• 通讯作者: 吉田松生

TBP-interacting protein 120b (TIP120B)/cullin-associated and neddylation-dissociated 2 (CAND2) inhibits SCF-dependent ubiquitination of myogenin and accelerates myogenic differentiaton

TBP 相互作用蛋白 120b (TIP120B)/cullin 相关和 neddylation 解离 2 (CAND2) 抑制 SCF 依赖性肌细胞生成素泛素化并加速肌原性分化

• 发表时间: 2007
• 期刊: Journal of Biological Chemistry 282
• 作者: S.Shiraishi;C.Zhou;T.Aoki;N.Sato;T.Chiba;K.Tanaka;S.Yoshida;Y.Nabeshima;Y-i.
• 通讯作者: Y-i.

TBP-interacting protein 120b (TIP120B) /cullin-associated and neddylation-dissociated 2 (CAND2) inhibits SCF-dependent ubiquitination of myogenin and accelerates myogenic differentiaton

TBP 相互作用蛋白 120b (TIP120B) /cullin 相关和 neddylation 解离 2 (CAND2) 抑制 SCF 依赖性肌细胞生成素泛素化并加速肌原性分化

• 发表时间: 2007
• 期刊: Journal of Biological Chemistry 282
• 作者: S.Shiraishi;C.Zhou;T.Aoki;N.Sato;T.Chiba;K.Tanaka;S.Yoshida;Y.Nabeshima;Y-i.Nabeshima;T.Tamura
• 通讯作者: T.Tamura