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Development and Differentiation of the Mouse Germ Cell Lineage; Mouse ES Cells and Germ Cells

摘要


The germ cell lineage in mammalian embryogenesis consists of the undifferentiated pluripotent stem cells in early embryos and germ cells originating as the primordial germ cells (PGCs). Such cells are important for investigation of the biological functions and also manipulation of mammalian genomes. We have been studying pluripotent stem cells and germ cells in culture to analyze regulative mechanisms of cell proliferation and differentiation along the germ cell lineage. Such culture system also enables experimental manipulation of the mammalian germ line. Various studies so for have revealed both common features and differences between the germ lineage cells at various developmental stages. We have established many ES cell lines from several inbred mouse strains including C57BL/6, MSM and SWN. The latter two strains had derived from wild mice in Japan and Korea, respectively, and they have various wild-type behavioral phenotypes different from ordinal laboratory mouse strains. Using such ES cells, we produced chimaeric mice that showed the germ line transmission from the ES cells. Also, we have been studying development of mouse germ cells in culture. PGCs isolated from embryos showed limited proliferation and autonomous growth arrest in culture. A combination of proliferation signals caused appearance of the EG cell colonies. Usage of antibodies against meiosis-specific proteins revealed that PGCs before and after arrival at female gonads autonomously enter into meiosis when cultured as dispersed single cells on a feeder cell layer. Even the male PGCs showed transition into meiosis in the same conditions. Using such culture system, we found that signals from LIF and its receptor gp130 caused strong inhibition of the meiotic entry PGCs in culture. Thus, the LIF/gp130 signal has multiple and probably related effects of the maintenance of undifferentiated stem cells, growth/survival of PGCs and inhibition of meiosis.

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