title: Toxic effects of cadmium on flatworm stem cell dynamics: A transcriptomic and ultrastructural elucidation of underlying mechanisms.
abstract: Stem cells or undifferentiated cells can cope more easily with external stresses. To evaluate the impact of toxic compounds on stem cell dynamics in vivo, in relation to other biological responses, we use the carcinogenic element cadmium and the regenerating model organism Macrostomum lignano. Through both BrdU and anti-histone H3 immunostainings, cadmium-induced effects were investigated at different stages of the stem cell cycle. A 24-h exposure to 100 and 250 μM CdCl2 significantly decreased the number of stem cells (neoblasts) in mitosis, whereas the number of cells in the S phase remained unchanged. After this short-term exposure, the ultrastructure of the neoblasts was minimally affected in contrast to the epidermal tissues. These results were supported by gene expression data: transcripts of cdc2 and pig3 were significantly upregulated during all treatments. Both genes are involved in the cell cycle progression and are transcribed in the gonadal region, where stem cells are highly represented. Based on a substantial increase in gene expression of heat shock proteins (HSP) and their high activity in the gonadal region, we hypothesize that these proteins are key players in the protection of stem cells against external stresses. Apart from the strong HSP induction, other protective processes including cell division, apoptosis and anti-oxidative defence, were also activated. We, therefore, conclude that the protection of stem cells against external stressors may be based on the interplay between stem cell maintenance, i.e. repair and recovery through division, on one hand and apoptosis on the other hand. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1217-1228, 2016.
authors.affiliation: Centre for Environmental Sciences, Department Biology, Hasselt University, Agoralaan, Diepenbeek, Belgium.
authors.forename: Michelle
authors.initials: M
authors.lastname: Plusquin
authors.affiliation: Institute of Zoology, Center of Molecular Bioscience Innsbruck, University of Innsbruck, Innrain, Innsbruck, Austria.
authors.forename: Katrien
authors.initials: K
authors.lastname: De Mulder
authors.affiliation: Centre for Environmental Sciences, Department Biology, Hasselt University, Agoralaan, Diepenbeek, Belgium.|Faculty of Management, Science and Technology, Open Universiteit, Valkenburgerweg 177, Heerlen, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Van Belleghem
authors.affiliation: Centre for Environmental Sciences, Department Biology, Hasselt University, Agoralaan, Diepenbeek, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: DeGheselle
authors.affiliation: Centre for Environmental Sciences, Department Biology, Hasselt University, Agoralaan, Diepenbeek, Belgium.
authors.forename: Nicky
authors.initials: N
authors.lastname: Pirotte
authors.affiliation: Pharmaceutical Technology, Ghent University, St. Pietersnieuwstraat, Gent, Belgium.
authors.forename: Maxime
authors.initials: M
authors.lastname: Willems
authors.affiliation: Centre for Environmental Sciences, Department Biology, Hasselt University, Agoralaan, Diepenbeek, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Cuypers
authors.affiliation: Institute of Zoology, Center of Molecular Bioscience Innsbruck, University of Innsbruck, Innrain, Innsbruck, Austria.
authors.forename: Willi
authors.initials: W
authors.lastname: Salvenmoser
authors.affiliation: Institute of Zoology, Center of Molecular Bioscience Innsbruck, University of Innsbruck, Innrain, Innsbruck, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Ladurner
authors.affiliation: Centre for Environmental Sciences, Department Biology, Hasselt University, Agoralaan, Diepenbeek, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Artois
authors.affiliation: Centre for Environmental Sciences, Department Biology, Hasselt University, Agoralaan, Diepenbeek, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Smeets
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000378:metabolism; D019256:Cadmium Chloride / Q000633:toxicity*; D004817:Epidermis / Q000187:drug effects / Q000648:ultrastructure; D006066:Gonads / Q000187:drug effects / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D017403:In Situ Hybridization; D008854:Microscopy, Electron; D008938:Mitosis / Q000187:drug effects; D010986:Platyhelminths / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016196:S Phase; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D006360:Heat-Shock Proteins; D006657:Histones; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; D016203:CDC2 Protein Kinase; D019256:Cadmium Chloride
keywords: Macrostomum lignano; cadmium; stem cell; stress; toxicology