Jagut Marlène, Huynh Jean-René
Institut Jacques-Monod, CNRS, Universités Paris 6 et 7, 2, place Jussieu, F-75251 Paris Cedex 05, France.
Med Sci (Paris). 2007 Jun-Jul;23(6-7):611-8. doi: 10.1051/medsci/20072367611.
Our fascination for stem cells originates from their ability to divide asymmetrically in order to self-renew and produce daughter cells which can differentiate and replenish tissues. Stem cells could thus represent an unlimited source of differentiated cells that could be used to repair malformed, damaged or ageing tissues. Understanding how their behaviour is regulated is then of paramount medical interest. Specific microenvironments surrounding the stem cells, termed "niches", were proposed to play a major role in the balance between self-renewal and differentiation. However, it is only recently, in the case of the stem cells producing the germline (GSGs) in Drosophila, that the cells and signals creating a niche were identified for the first time. Here, we review how this niche has been defined at the cellular and functional levels in vivo, thanks to the powerful genetic tools available in Drosophila. Such studies have revealed adhesive interactions, cell-cycle modifications and intercellular signals that control the GSC behavior. Extracellular signals from the niche activate the BMP or JAK-STAT pathways in the GSCs and are necessary for their maintenance. Strikingly, both signaling pathways are also sufficient to convert differentiated germ cells into functional GSCs, demonstrating in vivo that a niche has the capacity to regenerate stem cells from differentiated cells. Rapid progresses have further identified direct links between these signaling pathways and the transcriptional regulation of the GSCs, providing a simple paradigm for stem cells regulation. Many of these features and signals are conserved in stem cells niches from Drosophila to mammals. We can thus hope that research on the GSCs in Drosophila will benefit therapeutic approaches to human degenerative diseases.
我们对干细胞的着迷源于它们能够不对称分裂,从而实现自我更新并产生可分化并补充组织的子细胞。因此,干细胞可能代表了一种无限的分化细胞来源,可用于修复畸形、受损或老化的组织。了解它们的行为是如何被调控的,具有至关重要的医学意义。围绕干细胞的特定微环境,即所谓的“龛”,被认为在自我更新和分化之间的平衡中起主要作用。然而,直到最近,在果蝇中产生生殖系的干细胞(GSGs)的情况下,才首次确定了构成龛的细胞和信号。在这里,我们回顾了由于果蝇中可用的强大遗传工具,这个龛在体内是如何在细胞和功能水平上被定义的。此类研究揭示了控制GSG行为的黏附相互作用、细胞周期修饰和细胞间信号。来自龛的细胞外信号激活GSG中的BMP或JAK-STAT信号通路,并且是其维持所必需的。引人注目的是,这两种信号通路也足以将分化的生殖细胞转化为功能性GSG,在体内证明了龛具有从分化细胞再生干细胞的能力。快速的进展进一步确定了这些信号通路与GSG转录调控之间的直接联系,为干细胞调控提供了一个简单的范例。从果蝇到哺乳动物,这些特征和信号中的许多在干细胞龛中都是保守的。因此,我们可以希望对果蝇中GSG的研究将有益于人类退行性疾病的治疗方法。