Apontic regulates somatic stem cell numbers in Drosophila testes.
Apontic regulates somatic stem cell numbers in Drosophila testes.
复制标题
DOI：
10.1186/s12861-016-0103-3
复制
发表时间：
2016-03-18
影响因子：
--
通讯作者：
Starz-Gaiano M
中科院分区：
文献类型：
--
作者：
Monahan AJ;Starz-Gaiano M
微环境（niches）通过平衡自我更新与分化来维持常驻干细胞群，但这一过程的遗传调控尚不清楚。果蝇睾丸的生态位是很好的特点和遗传温顺，使其成为理想的研究干细胞生物学的分子调控。JAK/STAT通路由一个称为中枢的小生境组件的信号激活，维持生殖系和体干细胞。本研究探讨了果蝇睾丸干细胞中JAK/STAT通路的分子调控。我们确定转录调节因子Apt在体细胞（囊肿）干细胞（CySC）中起作用，以平衡分化和维持。我们发现Apt作为STAT活性的负反馈抑制剂发挥作用，这使得囊细胞成熟。STAT调节因子apt和Socs 36 E或Stat 92 E靶向microRNA miR-279的同时缺失，扩增了体干细胞样群体。遗传分析表明，一个保守的遗传调控网络限制了果蝇睾丸体干细胞中JAK/STAT的活性。在这些细胞中，我们确定JAK/STAT信号促进apt表达。然后，Apt通过Socs 36 E和miR-279发挥作用以减弱途径激活，这是及时CySC分化所需的。我们建议，Apt作为STAT调节回路的核心组成部分，以防止干细胞过度增殖，并允许干细胞成熟。本文的在线版本（doi：10.1186/s12861-016-0103-3）包含补充材料，可供授权用户使用。
Microenvironments called niches maintain resident stem cell populations by balancing self-renewal with differentiation, but the genetic regulation of this process is unclear. The niche of the Drosophila testis is well-characterized and genetically tractable, making it ideal for investigating the molecular regulation of stem cell biology. The JAK/STAT pathway, activated by signals from a niche component called the hub, maintains both germline and somatic stem cells. This study investigated the molecular regulation of the JAK/STAT pathway in the stem cells of the Drosophila testis. We determined that the transcriptional regulator Apontic (Apt) acts in the somatic (cyst) stem cells (CySCs) to balance differentiation and maintenance. We found Apt functions as a negative feedback inhibitor of STAT activity, which enables cyst cell maturation. Simultaneous loss of the STAT regulators apt and Socs36E, or the Stat92E-targeting microRNA miR-279, expanded the somatic stem cell-like population. Genetic analysis revealed that a conserved genetic regulatory network limits JAK/STAT activity in the somatic stem cells of Drosophila testis. In these cells, we determined JAK/STAT signaling promotes apt expression. Then, Apt functions through Socs36E and miR-279 to attenuate pathway activation, which is required for timely CySC differentiation. We propose that Apt acts as a core component of a STAT-regulatory circuit to prevent stem cell overpopulation and allow stem cell maturation. The online version of this article (doi:10.1186/s12861-016-0103-3) contains supplementary material, which is available to authorized users.