Developmental Genetics Program, Skirball Institute of Biomolecular Medicine, Helen and Martin Kimmel Center for Stem Cell Biology, and Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Curr Biol. 2012 Apr 24;22(8):712-9. doi: 10.1016/j.cub.2012.02.064. Epub 2012 Apr 5.
The proliferation/differentiation balance of stem and progenitor cell populations must respond to the physiological needs of the organism [1, 2]. Mechanisms underlying this plasticity are not well understood. The C. elegans germline provides a tractable system to study the influence of the environment on progenitor cells (stem cells and their proliferative progeny). Germline progenitors accumulate during larval stages to form an adult pool from which gametes are produced. Notch pathway signaling from the distal tip cell (DTC) niche to the germline maintains the progenitor pool [3-5], and the larval germline cell cycle is boosted by insulin/IGF-like receptor signaling [6]. Here we show that, independent of its role in the dauer decision, TGF-β regulates the balance of proliferation versus differentiation in the C. elegans germline in response to sensory cues that report population density and food abundance. Ciliated ASI sensory neurons are required for TGF-β-mediated expansion of the larval germline progenitor pool, and the TGF-β receptor pathway acts in the germline stem cell niche. TGF-β signaling thereby couples germline development to the quality of the environment, providing a novel cellular and molecular mechanism linking sensory experience of the environment to reproduction.
干细胞和祖细胞群体的增殖/分化平衡必须响应生物体的生理需求[1,2]。这种可塑性的基础机制尚不清楚。秀丽隐杆线虫的生殖系为研究环境对祖细胞(干细胞及其增殖后代)的影响提供了一个易于处理的系统。生殖系祖细胞在幼虫阶段积累,形成一个产生配子的成虫池。来自远端顶细胞(DTC)龛的 Notch 途径信号维持祖细胞池[3-5],并且幼虫生殖系细胞周期通过胰岛素/IGF 样受体信号[6]得到增强。在这里,我们表明,TGF-β 独立于其在 dauer 决策中的作用,通过报告种群密度和食物丰度的感觉线索,调节秀丽隐杆线虫生殖系中增殖与分化的平衡。有纤毛的 ASI 感觉神经元是 TGF-β 介导的幼虫生殖系祖细胞池扩张所必需的,TGF-β 受体途径在生殖干细胞龛中起作用。因此,TGF-β 信号将生殖系发育与环境质量联系起来,为将环境的感觉体验与繁殖联系起来提供了一种新的细胞和分子机制。