Competition for Mitogens Regulates Spermatogenic Stem Cell Homeostasis in an Open Niche.
Cell stem cell
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Kitadate, Y., Jörg, D. J., Tokue, M., Maruyama, A., Ichikawa, R., Tsuchiya, S., Segi-Nishida, E., et al. (2019). Competition for Mitogens Regulates Spermatogenic Stem Cell Homeostasis in an Open Niche.. Cell stem cell, 24 (1), 79-92.e6. https://doi.org/10.1016/j.stem.2018.11.013
In many tissues, homeostasis is maintained by physical contact between stem cells and an anatomically-defined niche. However, how stem cell homeostasis is achieved in environments where cells are motile and dispersed among their progeny remains unknown. Using murine spermatogenesis as a model, we find that spermatogenic stem cell density is tightly regulated by the supply of fibroblast growth factors (FGFs) from lymphatic endothelial cells. We propose that stem cell homeostasis is achieved through competition for a limited supply of FGFs. We show that the quantitative dependence of stem cell density on FGF dosage, the biased localization of stem cells towards FGF sources, and stem cell dynamics during regeneration following injury can all be predicted and explained within the framework of a minimal theoretical model based on “mitogen competition”. We propose that this model provides a generic and robust mechanism to support stem cell homeostasis in open, or facultative, niche environments.
Spermatozoa, Stem Cells, Animals, Mice, Inbred C57BL, Mice, Knockout, Mice, Mitogens, Cell Differentiation, Spermatogenesis, Homeostasis, Male, Glial Cell Line-Derived Neurotrophic Factor Receptors, Fibroblast Growth Factor 5, Cell Self Renewal
Wellcome Trust (098357/Z/12/Z)
Royal Society (RP/R1/180165)
Wellcome Trust (092096/Z/10/Z)
Cancer Research UK (A14492)
External DOI: https://doi.org/10.1016/j.stem.2018.11.013
This record's URL: https://www.repository.cam.ac.uk/handle/1810/288140
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/