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a Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, San Francisco, California;
b Departments of Physiology and
c Urology,
d Programs in Human Genetics, Cancer Genetics and Development, and Stem Cell Biology, University of California at San Francisco, San Francisco, California, USA
Key Words. Human embryonic stem cells • Pluripotent • Germ cell • OCT-4 • STELLAR • NANOG • GDF3 • Ovary • Testis • Embryonal carcinoma • Teratoma
Renee A. Reijo Pera, Ph.D., Center for Reproductive Sciences, HSE1656, Box 0556 UCSF, San Francisco, California 94143-0556, USA. Telephone: 415-476-3178; Fax: 415-476-3121; e-mail: reijo{at}itsa.ucsf.edu
Genes required to maintain pluripotency in human embryonic stem (hES) cells are largely unknown, with the exception of OCT-4, a homolog of mouse Oct-4, which is critical for the establishment of the embryonic inner cell mass and the generation of totipotent mouse embryonic stem (mES) cell lines. In the current study, we identified two genes with expression similar to OCT-4, in that they are largely restricted to pluripotent hES cells, premeiotic germ lineage cells, and testicular germ cell tumor cells. Furthermore, we determined that upon hES cell differentiation, their expression is downregulated. The genes we identified in the current study include the human stella-related (STELLAR) gene, which encodes a highly divergent protein (with just 32.1% identity to mouse stella over the 159 amino acid sequence) that maps to human chromosome 12p13. Notably, human STELLAR is located distal to a previously uncharacterized homeobox gene, which is the human homolog of the recently identified murine gene, Nanog, and proximal to the GDF3 locus, whose transcription is restricted to germ cell tumor cells. Our characterization of STELLAR, NANOG, and GDF3 suggests that they may play a similar role in humans as in mice, in spite of their remarkable evolutionary divergence.
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