Functional Hierarchy and Reversibility Within the Murine Spermatogenic Stem Cell Compartment
- Toshinori Nakagawa1,*,
- Manju Sharma2,
- Yo-ichi Nabeshima1,
- Robert E. Braun2 and
- Shosei Yoshida1,3,4,†
- 1Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
- 2The Jackson Laboratory, Bar Harbor, ME 04609, USA.
- 3Division of Germ Cell Biology, National Institute for Basic Biology, National Institutes for Natural Sciences, Okazaki 444-8787, Japan.
- 4Department of Basic Biology, School of Life Science, Graduate University for Advanced Studies (SOKENDAI), Okazaki 444-8585, Japan.
- †To whom correspondence should be addressed. E-mail: shosei{at}nibb.ac.jp
Abstract
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.
- Received for publication 5 October 2009.
- Accepted for publication 1 March 2010.
