The stem cell niche normally prevents aberrant stem cell behaviors that lead to cancer formation. Recent studies suggest that some cancers are derived from endogenous populations of adult stem cells that have somehow escaped from normal control by the niche. However, the molecular mechanisms by which the niche retains stem cells locally and tightly controls their divisions are poorly understood. Here, we demonstrate that the presence of heparan sulfate (HS), a class glygosaminoglycan chains, in the Drosophila germline stem cell niche prevents tumor formation in the testis. Loss of HS in the niche, called the hub, led to gross changes in the morphology of testes as well as the formation of both somatic and germline tumors. This loss of hub HS resulted in ectopic signaling events in the Jak/Stat pathway outside the niche. This ectopic Jak/Stat signaling disrupted normal somatic cell differentiation, leading to the formation of tumors. Our finding indicates a novel non-autonomous role for niche HS in ensuring the integrity of the niche and preventing tumor formation.

中文翻译：

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微环境中硫酸乙酰肝素的损失导致果蝇睾丸中肿瘤样生殖细胞的生长


干细胞生态位通常可以防止导致癌症形成的异常干细胞行为。最近的研究表明，一些癌症源自成体干细胞的内源性群体，这些细胞以某种方式逃脱了生态位的正常控制。然而，人们对微环境在局部保留干细胞并严格控制其分裂的分子机制知之甚少。在这里，我们证明果蝇生殖干细胞微环境中硫酸乙酰肝素（HS）（一类糖胺聚糖链）的存在可以防止睾丸中肿瘤的形成。称为中枢的微环境中 HS 的丢失导致睾丸形态的总体变化以及体细胞和种系肿瘤的形成。中枢 HS 的丢失导致微生境外 Jak/Stat 通路中的异位信号事件。这种异位 Jak/Stat 信号传导破坏了正常的体细胞分化，导致肿瘤的形成。我们的发现表明利基 HS 在确保利基完整性和预防肿瘤形成方面具有新的非自主作用。