Stem cells are tightly controlled in vivo. Both the balance between self-renewal and differentiation and the rate of proliferation are often regulated by multiple factors. The Caenorhabditis elegans hermaphrodite germ line provides a simple and accessible system for studying stem cells in vivo. In this system, GLP-1/Notch activity prevents the differentiation of distal germ cells in response to ligand production from the nearby distal tip cell, thereby supporting a stem cell pool. However, a delay in germline development relative to somatic gonad development can cause a pool of undifferentiated germ cells to persist in response to alternate Notch ligands expressed in the proximal somatic gonad. This pool of undifferentiated germ cells forms a proximal tumor that, in adulthood, blocks the oviduct. This type of "latent niche"-driven proximal tumor is highly penetrant in worms bearing the temperature-sensitive weak gain-of-function mutation glp-1(ar202) at the restrictive temperature. At the permissive temperature, few worms develop tumors. Nevertheless, several interventions elevate the penetrance of proximal tumor formation at the permissive temperature, including reduced insulin signaling or the ablation of distal-most sheath cells. To systematically identify genetic perturbations that enhance proximal tumor formation, we sought genes that, upon RNAi depletion, elevate the percentage of worms bearing proximal germline tumors in glp-1(ar202) at the permissive temperature. We identified 43 genes representing a variety of functional classes, the most enriched of which is "translation". Some of these genes also influence the distal germ line, and some are conserved genes for which genetic interactions with Notch were not previously known in this system.

干细胞在体内受到严格控制。自我更新和分化之间的平衡以及增殖速率通常都受多种因素调节。在秀丽隐杆线虫雌雄同体种系为研究干细胞的简单和方便系统在体内。在该系统中，GLP-1 / Notch活性可防止远端生殖细胞分化，以响应附近远端尖端细胞产生的配体，从而支持干细胞库。然而，生殖细胞发育相对于体细胞性腺发育的延迟会导致未分化的生殖细胞池持续响应近端体细胞性腺中表达的Notch配体。未分化的生殖细胞池形成近端肿瘤，成年后阻塞输卵管。这种类型的“潜伏小生境”驱动的近端肿瘤在带有温度敏感性弱功能获得突变glp-1的蠕虫中高度渗透（ar202）在极限温度下。在允许的温度下，很少有蠕虫会形成肿瘤。然而，一些干预措施在允许的温度下提高了近端肿瘤形成的渗透性，包括降低胰岛素信号传导或消除最远端的鞘细胞。为了系统地识别增强近端肿瘤形成的遗传扰动，我们寻求了在RNAi耗尽后可在允许温度下提高glp-1（ar202）中带有近端种系肿瘤的蠕虫百分比的基因。我们鉴定了代表各种功能类别的43个基因，其中最丰富的是“翻译”。这些基因中的一些也影响远端生殖细胞系，而一些是保守的基因，在该系统中以前不知道与Notch的遗传相互作用。