International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA



11.45am – 12.00pm


Abe K1, Sugimoto M1, Kobayakawa S1, Noce T2, Qian Y3, Sharov A3, Ko M3, Mise N1

1 RIKEN BRC, Tsukuba, Japan, 2 Mitsubishi Inst Life Sci, Tokyo, Japan, 3 National Inst on Aging, Baltimore, United States

In developing mammalian early embryos, there exist pluripotent stem cells, giving rise to all somatic cells as well as germ line cells. Primordial germ cell (PGC) is the cell-type appeared first in the germ cell lineage, sharing many features with the embryonic stem cells. Unlike differentiated somatic cells, the PGCs possess ability to erase epigenetic modifications on the genome accumulated during development. Thus PGCs can be regarded as the cells programmed to rejuvenate the genomic status. Despite of this biological importance, molecular nature of the PGCs remains largely unknown. We have established systematic methodologies to analyze PGCs and related embryonic cells: PGCs were purified from transgenic mouse embryos, in which the PGCs were marked by GFP-reporter expression, and cDNA libraries were made with the purified PGCs; transcriptome of the PGCs were explored by EST analyses and microarray. ESTs were classified according to the NIA Mouse Gene Index: the analyzed 18,293 ESTs were clustered into 6,159 transcripts and 4,833 genes, of which 435 were unknown genes. Analysis of EST frequency suggested expression level of each gene, and identified 'signature' genes for PGCs. Principal component analysis of EST frequency showed that PGCs are more similar to blastocyst or Trophoblast stem (TS) cells rather than undifferentiated ES cells or embryonic germ (EG) cells, which were derived from PGCs.

We compared gene expression profiles of ES, EG, PGC, and PGC-like cells derived from ES cells in vitro (Toyooka et al., 2003). EG cells have an expression profile quite similar to that of ES cells (only 1-2% of about 20,000 genes showed significant differences ), although EG cells are different from ES cells in terms of genome-reprogramming activity (Tada et al., 1997). In contrast, PGCs have an expression program distinct from ES cells: for example, about 17% of genes showed differences between ES and E13.5 female PGCs, suggesting that dynamic changes in gene expression occur during establishment of germ cell lineage from undifferentiated stem cells. Comparisons of PGCs with the in vitro-formed PGCs identified a set of genes that characterize PGC development. 

Knowledge and resources obtained in this study should facilitate a wide range of research in germ cell and stem cell biology.

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