The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, Toronto, Ontario, Canada.
University of Toronto, Department of Molecular Genetics, Toronto, Ontario, Canada.
PLoS Genet. 2020 Feb 20;16(2):e1008613. doi: 10.1371/journal.pgen.1008613. eCollection 2020 Feb.
The extracellular matrix (ECM) is important for maintaining the boundaries between tissues. This role is particularly critical in the stem cell niche, as pre-neoplastic or cancerous stem cells must pass these boundaries in order to invade into the surrounding tissue. Here, we examine the role of the ECM as a regulator of the stem cell compartment in the planarian Schmidtea mediterranea, a highly regenerative, long-lived organism with a large population of adult stem cells. We identify two EGF repeat-containing genes, megf6 and hemicentin, with identical knockdown phenotypes. We find that megf6 and hemicentin are needed to maintain the structure of the basal lamina, and in the absence of either gene, pluripotent stem cells migrate ectopically outside of their compartment and hyper-proliferate, causing lesions in the body wall muscle. These muscle lesions and ectopic stem cells are also associated with ectopic gut branches, which protrude from the normal gut towards the dorsal side of the animal. Interestingly, both megf6 and hemicentin knockdown worms are capable of regenerating tissue free of both muscle lesions and ectopic cells, indicating that these genes are dispensable for regeneration. These results provide insight into the role of planarian ECM in restricting the stem cell compartment, and suggest that signals within the compartment may act to suppress stem cell hyperproliferation.
细胞外基质（ECM）对于维持组织之间的边界很重要。在干细胞龛中，这一作用尤为关键，因为前肿瘤或癌变的干细胞必须通过这些边界才能侵入周围组织。在这里，我们研究了 ECM 作为扁形动物地中海滨螺（Schmidtea mediterranea）干细胞区室调节剂的作用，该动物具有高度再生性、长寿命和大量成年干细胞。我们鉴定出了两个含有 EGF 重复的基因，megf6 和 hemicentin，它们具有相同的敲低表型。我们发现 megf6 和 hemicentin 对于维持基底层的结构是必需的，在这两个基因都缺失的情况下，多能干细胞会异位迁移到它们所在的区室外，并过度增殖，导致体壁肌肉出现损伤。这些肌肉损伤和异位干细胞也与异位的肠道分支有关，这些分支从正常肠道向动物的背部伸出。有趣的是，megf6 和 hemicentin 敲低的线虫都能够再生没有肌肉损伤和异位细胞的组织，这表明这些基因对于再生是可有可无的。这些结果提供了关于扁形动物 ECM 在限制干细胞区室方面的作用的见解，并表明区室内的信号可能会抑制干细胞的过度增殖。
