Dedifferentiating spermatogonia outcompete somatic stem cells for niche occupancy in the Drosophila testis.
Dedifferentiating spermatogonia outcompete somatic stem cells for niche occupancy in the Drosophila testis.
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DOI：
10.1016/j.stem.2009.05.024
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发表时间：
2009-08-07
期刊：
影响因子：
23.9
通讯作者：
Matunis EL
中科院分区：
文献类型：
--
作者：
Sheng XR;Brawley CM;Matunis EL
分化细胞可以去分化以取代衰老或受损组织中的干细胞，但其潜在机制尚不清楚。在果蝇睾丸中，一群称为枢纽的基质细胞通过局部激活邻近生殖系和体干细胞中的Janus激酶、信号转导和转录激活因子（Jak-STAT）信号传导来创建一个小生境。本文建立了一个研究精原细胞脱分化的新体系。异位表达的分化因子Bag-of-marbles（BAM）将生殖系干细胞从小生境中移除。然而，取出异位Bam会导致相互连接的精原细胞破碎，移动到龛中，与驻留的体干细胞交换位置并与枢纽建立联系。同时，肌动蛋白为基础的突起出现在精原细胞的子集，表明获得性运动。此外，Jak-STAT信号传导的全局下调抑制去分化，表明在去分化期间需要正常水平的通路激活来促进精原细胞移动到生态位中，在那里它们竞争超过体干细胞的生态位占据。
Differentiating cells can dedifferentiate to replace stem cells in aged or damaged tissues, but the underlying mechanisms are unknown. In the Drosophila testis a cluster of stromal cells called the hub creates a niche by locally activating Janus-Kinase, Signal Transducer and Activator of Transcription (Jak-STAT) signaling in adjacent germline and somatic stem cells. Here we establish a novel system to study spermatogonial dedifferentiation. Ectopically expressing the differentiation factor Bag-of-marbles (Bam) removes germline stem cells from the niche. However, withdrawing ectopic Bam causes interconnected spermatogonia to fragment, move into the niche, exchange positions with resident somatic stem cells and establish contact with the hub. Concomitantly, Actin-based protrusions appear on subsets of spermatogonia, suggesting acquired motility. Furthermore, global downregulation of Jak-STAT signaling inhibits dedifferentiation, indicating that normal levels of pathway activation are required to promote movement of spermatogonia into the niche during dedifferentiation, where they outcompete somatic stem cells for niche occupancy.
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