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Competition for Mitogens Regulates Spermatogenic Stem Cell Homeostasis in an Open Niche.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Kitadate, Yu 
Jörg, David J 
Tokue, Moe 
Maruyama, Ayumi 
Ichikawa, Rie 

Abstract

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 toward 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.

Description

Keywords

biophysical modeling, density homeostasis, fibroblast growth factors, mitogen competition, open niche, spermatogenesis, stem cells, Animals, Cell Differentiation, Cell Self Renewal, Fibroblast Growth Factor 5, Glial Cell Line-Derived Neurotrophic Factor Receptors, Homeostasis, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitogens, Spermatogenesis, Spermatozoa, Stem Cells

Journal Title

Cell Stem Cell

Conference Name

Journal ISSN

1934-5909
1875-9777

Volume Title

24

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (098357/Z/12/Z)
Royal Society (RP/R1/180165)
Medical Research Council (MC_PC_12009)
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)
Wellcome Trust