Planarian EGF repeat-containing genes megf6 and hemicentin are required to restrict the stem cell compartment


Autoři: Nicole Lindsay-Mosher aff001;  Andy Chan aff001;  Bret J. Pearson aff001
Působiště autorů: The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, Toronto, Ontario, Canada aff001;  University of Toronto, Department of Molecular Genetics, Toronto, Ontario, Canada aff002;  Ontario Institute for Cancer Research, Toronto, Ontario, Canada aff003;  School of Biomedical Sciences, LKS Faculty of Medicine, Pokfulam, Hong Kong SAR, China aff003;  Ontario Institute for Cancer Research, Toronto, Ontario, Canada aff004
Vyšlo v časopise: Planarian EGF repeat-containing genes megf6 and hemicentin are required to restrict the stem cell compartment. PLoS Genet 16(2): e32767. doi:10.1371/journal.pgen.1008613
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008613

Souhrn

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.

Klíčová slova:

Epidermis – Muscle fibers – Pigments – Planarians – RNA interference – Stem cells – Stem cell niche – Basement membrane


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Genetika Reprodukční medicína

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