Feedback control in planarian stem cell systems

Mangel, Marc; Bonsall, Michael B.; Aboobaker, Aziz
February 2016
BMC Systems Biology;2/13/2016, Vol. 10, p1
Academic Journal
Background: In planarian flatworms, the mechanisms underlying the activity of collectively pluripotent adult stem cells (neoblasts) and their descendants can now be studied from the level of the individual gene to the entire animal. Flatworms maintain startling developmental plasticity and regenerative capacity in response to variable nutrient conditions or injury. We develop a model for cell dynamics in such animals, assuming that fully differentiated cells exert feedback control on neoblast activity. Results: Our model predicts a number of whole organism level and general cell biological and behaviours, some of which have been empirically observed or inferred in planarians and others that have not. As previously observed empirically we find: 1) a curvilinear relationship between external food and planarian steady state size; 2) the fraction of neoblasts in the steady state is constant regardless of planarian size; 3) a burst of controlled apoptosis during regeneration after amputation as the number of differentiated cells are adjusted towards their homeostatic/steady state level. In addition our model describes the following properties that can inform and be tested by future experiments: 4) the strength of feedback control from differentiated cells to neoblasts (i.e. the activity of the signalling system) and from neoblasts on themselves in relation to absolute number depends upon the level of food in the environment; 5) planarians adjust size when food level reduces initially through increased apoptosis and then through a reduction in neoblast self-renewal activity; 6) following wounding or excision of differentiated cells, different time scales characterize both recovery of size and the two feedback functions; 7) the temporal pattern of feedback controls differs noticeably during recovery from a removal or neoblasts or a removal of differentiated cells; 8) the signaling strength for apoptosis of differentiated cells depends upon both the absolute and relative deviations of the number of differentiated cells from their homeostatic level; and 9) planaria prioritize resource use for cell divisions. Conclusions: We offer the first analytical framework for organizing experiments on planarian flatworm stem cell dynamics in a form that allows models to be compared with quantitative cell data based on underlying molecular mechanisms and thus facilitate the interplay between empirical studies and modeling. This framework is the foundation for studying cell migration during wound repair, the determination of homeostatic levels of differentiated cells by natural selection, and stochastic effects.


Related Articles

  • Stem cell proliferation during in vitro development of the model cestode Mesocestoides corti from larva to adult worm. Koziol, Uriel; Domínguez, María F.; Marín, Mónica; Kun, Alejandra; Castillo, Estela // Frontiers in Zoology;2010, Vol. 7, p22 

    Background: In free-living flatworms somatic differentiated cells do not divide, and a separate population of stem cells (called neoblasts) is responsible for cell proliferation and renewal. In cestodes, there is evidence that similar mechanisms of cell renewal exist. Results: In this work, we...

  • Stem Cells Propagate Their DNA by Random Segregation in the Flatworm Macrostomum lignano. Verdoodt, Freija; Willems, Maxime; Mouton, Stijn; Mulder, Katrien De; Bert, Wim; Houthoofd, Wouter; Smith III, Julian; Ladurner, Peter // PLoS ONE;Jan2012, Vol. 7 Issue 1, p1 

    Adult stem cells are proposed to have acquired special features to prevent an accumulation of DNA-replication errors. Two such mechanisms, frequently suggested to serve this goal are cellular quiescence, and non-random segregation of DNA strands during stem cell division, a theory designated as...

  • Evidence that stem cells reside in the adult Drosophila midgut epithelium. Micchelli, Craig A.; Perrimon, Norbert // Nature;1/26/2006, Vol. 439 Issue 7075, p475 

    Adult stem cells maintain organ systems throughout the course of life and facilitate repair after injury or disease. A fundamental property of stem and progenitor cell division is the capacity to retain a proliferative state or generate differentiated daughter cells; however, little is currently...

  • Concise Review: Asymmetric Cell Divisions in Stem Cell Biology. Murke, Florian; da Conceição Castro, Symone Vitoriano; Giebel, Bernd; Görgens, André // Symmetry (20738994);2015, Vol. 7 Issue 4, p2025 

    Somatic stem cells are rare cells with unique properties residing in many organs and tissues. They are undifferentiated cells responsible for tissue regeneration and homeostasis, and contain both the capacity to self-renew in order to maintain their stem cell potential and to differentiate...

  • Differential Localization of mRNAs During Early Development in the Mollusc, Crepidula fornicata. Henry, Jonathan J.; Perry, Kimberly J.; Fukui, Lisa; Alvi, Nazia // Integrative & Comparative Biology;Nov2010, Vol. 50 Issue 5, p720 

    Certain mRNAs have been shown to be segregated in different cells in various metazoan embryos. These events represent aspects of autonomous mechanisms that establish particular embryonic cell fates and axial properties associated with asymmetric cell divisions. The spiralian lophotrochozoans...

  • Stem cells: To be and not to be. Lin, Haifan // Nature;9/25/2003, Vol. 425 Issue 6956, p353 

    Illustrates the molecular basis of stem cells' division to generate an identical daughter cell and a cell that becomes more specialized. Distinctive asymmetry in the division of stem cells; Factors that hinder the study of how stem cells divide.

  • Non-stop division of ES cells is regulated by a microRNA pathway.  // Reproductive BioMedicine Online (Reproductive Healthcare Limited;Feb2006, Vol. 12 Issue 2, p204 

    The article discusses various research being done on the regulation of the non-stop division of embryo stem (ES) cells. It is noted that studies involving Drosophila have revealed how the microRNA pathway (miRNA) controls the division of germline stem cells. Further explanations on how microRNA...

  • Lgl, Pins and aPKC regulate neuroblast self-renewal versus differentiation. Cheng-Yu Lee; Robinson, Kristin J.; Doe, Chris Q. // Nature;2/2/2006, Vol. 439 Issue 7076, p594 

    How a cell chooses to proliferate or to differentiate is an important issue in stem cell and cancer biology. Drosophila neuroblasts undergo self-renewal with every cell division, producing another neuroblast and a differentiating daughter cell, but the mechanisms controlling the...

  • Molecular Image Analysis: Quantitative Description and Classification of the Nuclear Lamina in Human Mesenchymal Stem Cells. Righolt, Christiaan H.; Raz, Vered; Vermolen, Bart J.; Dirks, Roeland W.; Tanke, Hans J.; Young, Ian T. // International Journal of Molecular Imaging;2011, p1 

    The nuclear lamina is an intermediate filament network that provides a structural framework for the cell nucleus. Changes in lamina structure are found during changes in cell fate such as cell division or cell death and are associated with human diseases. An unbiased method that quantifies...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics