Research Article

Functional Hierarchy and Reversibility Within the Murine Spermatogenic Stem Cell Compartment

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Science  18 Mar 2010:
DOI: 10.1126/science.1182868


Stem cells support tissue maintenance by balancing self-renewal and differentiation. In mice, it is believed that a homogeneous stem cell population of single spermatogonia supports spermatogenesis, and that differentiation, which is accompanied by the formation of connected cells (cysts) of increasing length, is linear and nonreversible. We evaluated this model using lineage-analysis and live-imaging and found that this putative stem cell population is not homogeneous. Instead, the stem cell pool that supports steady-state spermatogenesis is contained within a subpopulation of single spermatogonia. Also, cysts are not committed to differentiation and appear to recover stem cell potential by fragmentation. Lastly, the fate of individual spermatogonial populations was dramatically altered during regeneration following damage. Thus, there are multiple and reversible paths from stem cell to differentiation, which may also occur in other systems.