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Title: | Planarians Customize Their Stem Cell Responses Following Genotoxic Stress as a Function of Exposure Time and Regenerative State | Authors: | STEVENS, An-Sofie WOUTERS, Annelies PLOEM, Jan-Pieter PIROTTE, Nicky VAN ROTEN, Andromeda WILLEMS, Maxime Franken, Carmen Koppen, Gudrun HELLINGS, Niels ARTOIS, Tom PLUSQUIN, Michelle SMEETS, Karen |
Issue Date: | 2018 | Source: | TOXICOLOGICAL SCIENCES, 162(1), p. 251-263 | Abstract: | Aiming to in vivo characterize the responses of pluripotent stem cells and regenerative tissues to carcinogenic stress, we employed the highly regenerative organism Schmidtea mediterranea. Its broad regenerative capacities are attributable to a large pool of pluripotent stem cells, which are considered key players in the lower vulnerability toward chemically induced carcinogenesis observed in regenerative organisms. Schmidtea mediterranea is, therefore, an ideal model to study pluripotent stem cell responses with stem cells residing in their natural environment. Including microenvironmental alterations is important, as the surrounding niche influences the onset of oncogenic events. Both short-(3 days) and long-term (17 days) exposures to the genotoxic carcinogen methyl methanesulfonate (50 mu M) were evaluated during homeostasis and animal regeneration, two situations that render altered cellular niches. In both cases, MMS-induced DNA damage was observed, which provoked a decrease in proliferation on the short term. The outcome of DNA damage responses following long-term exposure differed between homeostatic and regenerating animals. During regeneration, DNA repair systems were more easily activated than in animals in homeostasis, where apoptosis was an important outcome. Knockdown experiments confirmed the importance of DNA repair systems during carcinogenic exposure in regenerating animals as knockdown of rad51 induced a stem cell-depleted phenotype, after regeneration was completed. | Notes: | Smeets, K (reprint author), Hasselt Univ, Zool Biodivers & Toxicol, Ctr Environm Sci, Agoralaan,Bldg D, B-3590 Diepenbeek, Belgium, karen.smeets@uhasselt.be | Keywords: | planarians; regeneration; stem cells; genotoxicity; DNA damage response | Document URI: | http://hdl.handle.net/1942/26279 | ISSN: | 1096-6080 | e-ISSN: | 1096-0929 | DOI: | 10.1093/toxsci/kfx247 | ISI #: | 000427020900025 | Rights: | © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2019 |
Appears in Collections: | Research publications |
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stevens2017.pdf | Peer-reviewed author version | 1.27 MB | Adobe PDF | View/Open |
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