Phenotypic plasticity of mouse spermatogonial stem cells.
BACKGROUND
Spermatogonial stem cells (SSCs) continuously undergo self-renewal division to support spermatogenesis. SSCs are thought to have a fixed phenotype, and development of a germ cell transplantation technique facilitated their characterization and prospective isolation in a deterministic manner; however, our in vitro SSC culture experiments indicated heterogeneity of cultured cells and suggested that they might not follow deterministic fate commitment in vitro.


RESULTS
In this study, we report phenotypic plasticity of SSCs. Although c-kit tyrosine kinase receptor (Kit) is not expressed in SSCs in vivo, it was upregulated when SSCs were cultured on laminin in vitro. Both Kit(-) and Kit(+) cells in culture showed comparable levels of SSC activity after germ cell transplantation. Unlike differentiating spermatogonia that depend on Kit for survival and proliferation, Kit expressed on SSCs did not play any role in SSC self-renewal. Moreover, Kit expression on SSCs changed dynamically once proliferation began after germ cell transplantation in vivo.


CONCLUSIONS
These results indicate that SSCs can change their phenotype according to their microenvironment and stochastically express Kit. Our results also suggest that activated and non-activated SSCs show distinct phenotypes.
Morimoto
Hiroko
H
Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kanatsu-Shinohara
Mito
M
Takashima
Seiji
S
Chuma
Shinichiro
S
Nakatsuji
Norio
N
Takehashi
Masanori
M
Shinohara
Takashi
T
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D017690:Cell Transplantation; D003433:Crosses, Genetic; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013093:Spermatogonia / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*
D049452:Green Fluorescent Proteins; D019009:Proto-Oncogene Proteins c-kit