Mouse Germ Line Stem Cells Undergo Rapid and Stochastic Turnover

SummaryIn cycling tissues, adult stem cells may be lost and subsequently replaced to ensure homeostasis. To examine the frequency of stem cell replacement, we analyzed the population dynamics of labeled stem cells in steady-state mouse spermatogenesis. Our results show that spermatogenic stem cells are continuously replaced, on average within 2 weeks. The analysis exposes a simple and robust scaling behavior of clone size distributions that shows stem cell replacement to be stochastic, meaning that stem cells are equipotent and equally likely to be lost or to multiply to replace their neighbors, irrespective of their clonal history. The surprisingly fast rate of stem cell replacement is supported experimentally by 3D clone morphology and by live-imaging of spermatogonial migration. These results suggest that short-lived stem cells may be a common feature of mammalian stem cell systems and reveal a natural mechanism for matching the rates of cell proliferation and loss in tissue.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (171 K)Download as PowerPoint slideHighlights► Spermatogonial clones reveal ongoing replacement of stem cells by their neighbors ► A scaling analysis of clone fate reveals the pattern of stem cell replacement ► Stem cell loss and replacement follows an average lifetime of less than 2 weeks ► Stem cells are equipotent, as replacement is random and any stem cell may be lost