Department of Developmental Biology, School of Medicine, Stanford University, Stanford, California, United States of America.
PLoS One. 2012;7(12):e52892. doi: 10.1371/journal.pone.0052892. Epub 2012 Dec 21.
Adult stem cells are essential for the proper function of many tissues, yet the mechanisms that maintain the proper identity and regulate proliferative capacity in stem cell lineages are not well understood. Polycomb group (PcG) proteins are transcriptional repressors that have recently emerged as important regulators of stem cell maintenance and differentiation. Here we describe the role of Polycomb Repressive Complex 1 (PRC1) genes Posterior sex combs (Psc) and Suppressor of zeste two (Su(z)2) in restricting the proliferation and maintaining the identity of the Cyst Stem Cell (CySC) lineage in the Drosophila testis. In contrast, Psc and Su(z)2 seem to be dispensable for both germline stem cell (GSC) maintenance and germ cell development. We show that loss of Psc and Su(z)2 function in the CySC lineage results in the formation of aggregates of mutant cells that proliferate abnormally, and display abnormal somatic identity correlated with derepression of the Hox gene Abdominal-B. Furthermore, we show that tumorigenesis in the CySC lineage interferes non-cell autonomously with maintenance of GSCs most likely by displacing them from their niche.
成体干细胞对于许多组织的正常功能至关重要,但维持干细胞谱系适当身份和调节增殖能力的机制尚未得到很好的理解。多梳组(PcG)蛋白是转录抑制剂,最近被认为是干细胞维持和分化的重要调节剂。在这里,我们描述了 Polycomb Repressive Complex 1 (PRC1) 基因 Posterior sex combs (Psc) 和 Suppressor of zeste two (Su(z)2) 在限制果蝇睾丸中的 Cyst Stem Cell (CySC) 谱系增殖和维持其身份中的作用。相比之下,Psc 和 Su(z)2 似乎对生殖干细胞 (GSC) 的维持和生殖细胞的发育都不是必需的。我们表明,在 CySC 谱系中丧失 Psc 和 Su(z)2 的功能会导致突变细胞异常增殖的聚集体的形成,并显示与 Hox 基因 Abdominal-B 去抑制相关的异常体身份。此外,我们表明 CySC 谱系中的肿瘤发生通过将它们从其龛位中置换出来,非细胞自主地干扰 GSCs 的维持。