Phenotypic plasticity of mouse spermatogonial stem cells

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...

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Bibliographic Details
Published in:PloS one 2009-11, Vol.4 (11), p.e7909-e7909
Main Authors: Morimoto, Hiroko, Kanatsu-Shinohara, Mito, Takashima, Seiji, Chuma, Shinichiro, Nakatsuji, Norio, Takehashi, Masanori, Shinohara, Takashi
Format: Article
Language:English
Subjects:
Animals
c-Kit protein
Cell culture
Cell Differentiation
Cell growth
Cell Lineage
Cell self-renewal
Cell survival
Cell Transplantation
Crosses, Genetic
Cytotoxicity
Developmental Biology/Cell Differentiation
Developmental Biology/Germ Cells
Developmental Biology/Stem Cells
Gene Expression Regulation
Genetics
Green Fluorescent Proteins - metabolism
In vitro methods and tests
Infertility
Laminin
Male
Medicine
Mice
Mice, Inbred C57BL
Mice, Transgenic
Models, Biological
Mutagenesis
Phenotype
Phenotypic plasticity
Plastic properties
Plasticity
Protein-tyrosine kinase receptors
Proto-Oncogene Proteins c-kit - metabolism
Rodents
Spermatogenesis
Spermatogonia
Spermatogonia - cytology
Spermatogonia - metabolism
Stem cell transplantation
Stem cells
Stem Cells - cytology
Transplantation
Tyrosine
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Summary: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. 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. 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0007909