Aging Cell：袭荣文实验室干细胞研究新成果

2008年2月11日，北京生命科学研究所袭荣文实验室在Aging Cell杂志上在线发表题为“Age-related changes of germline stem cell activity, niche signaling activity and egg production in Drosophila”的文章。

该文章报道了年龄因素对果蝇卵巢内生殖干细胞的小生境(niche)的功能的影响，及由此造成的干细胞的活性及生育能力的变化。

随着年龄的增长，存在于许多组织和器官的干细胞的活性有一种衰退的现象，表现在组织器官的再生及修复能力的下降。但是干细胞衰老的机制很不清楚。在这项工作中，研究者利用果蝇的卵形成作为一个干细胞模式系统，全面的分析了年龄引起的生殖干细胞的数量及活性，小生境的功能，干细胞内小生境信号通路的活性，卵巢管数目及产卵量等的变化，并通过遗传学方法研究了改变小生境信号因子的分泌量对干细胞活性及产卵量的影响。发现了干细胞活性随着年龄的增长迅速降低，伴随着控制干细胞的一个重要的小生境BMP信号的减弱。增强BMP信号可以延缓干细胞的衰老，并短暂促进产卵量的上升。研究者还发现随着年龄的增长，发育中的卵的死亡率迅速上升，促使了产卵量的下降。

这项研究与最近的两项研究（Boyle et al, Pan et al, Cell Stem Cell, Vol 2,2007）一起，最早发现了果蝇生殖干细胞小生境的衰老现象，揭示了微环境的改变是干细胞衰老的一个重要机制。不同的是，这项工作同时包括了小生境衰老对干细胞活性和生育能力的影响，并发现了影响后者的两个重要因素：干细胞活性及发育中卵的死亡率，而后者成为年老雌蝇产卵量下降的一个决定性因素，提示组织器官的老化不能单纯归结为干细胞能力的下降。

赵瑞（博士生）为本文的第一作者。其他作者还有宣扬和李兴华。袭荣文博士为本文通讯作者。此项研究为科技部863和北京市科委资助课题，在北京生命科学研究所完成。（北京生命科学研究所）

生物谷推荐原始出处：

Aging Cell

OnlineAccepted Articles (Accepted, unedited articles or abstracts published online for future issues)

To cite this article: Rui Zhao, Yang Xuan, Xinghua Li, Rongwen Xi (2008)
Age-related changes of germline stem cell activity, niche signaling activity and egg production in Drosophila
doi:10.1111/j.1474-9726.2008.00379.x
(Online Accepted)

Age-related changes of germline stem cell activity, niche signaling activity and egg production in Drosophila

Rui Zhao,
Yang Xuan,
Xinghua Li &
Rongwen Xi**corresponding author: National Institute of Biological Sciences No. 7 Science Park Road Zhongguancun Life Science Park Beijing 102206, China Tel: 86-10-80723241 Fax: 86-10-80723249 E-mail: xirongwen@nibs.ac.cn

National Institute of Biological Sciences (NIBS), Beijing 102206, China

*corresponding author: National Institute of Biological Sciences No. 7 Science Park Road Zhongguancun Life Science Park Beijing 102206, China Tel: 86-10-80723241 Fax: 86-10-80723249 E-mail: xirongwen@nibs.ac.cn

Summary

Adult stem cells are important in replenishing aged cells to maintain tissue homeostasis. Aging in turn may exert profound effects on stem cell’s regenerative potential, but to date the mechanisms of such stem cell aging are poorly understood, and it is not clear to what extent stem cell aging contributes to tissue or organ aging. Here we show in female Drosophila, that germline stem cell (GSC) division rate progressively declines with age, which is accompanied by reduced decapentaplegic (dpp) niche signaling pathway activation within GSCs. Egg production also rapidly declines with age, which is accompanied by both decreased stem cell division and increased incidence of cell death of developing eggs, especially in the oldest females. Genetically increasing dpp expression delays GSC activity decline and transiently increases egg production. We conclude that age-related decline of reproduction is caused by both decreased GSC activity and increased incidence of cell death during oogenesis, while decreased GSC activity is attributed to declined signaling from the regulatory niche. We suggest that niche functional decay may be an important mechanism for stem cell aging and system failure.