Competition for mitogens regulates spermatogenic stem cell homeostasis in an open niche

Kitadate Y et al. (2018) Cell Stem Cell Dec 11. pii: S1934-5909(18)30549-6. DOI: 10.1016/j.stem.2018.11.013. [Epub ahead of print]

Highlights from the paper 

• Mouse spermatogenic stem cells (SSCs) migrate among their differentiating progeny
• Lymphatic endothelial cells near vasculature secrete fibroblast growth factors (FGFs) that act as SSC mitogens
• SSCs tune their self-renewal and differentiation in response to FGF consumption
• Competition for limited supply of mitogen regulates SSC density homeostasis

Summary from the paper 

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.

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