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EMBRYONIC STEM CELLS |
aInstitute for Cellular Engineering, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA;
bDepartment of Gynecology and Obstetrics, Stanford University, Stanford, California, USA
Key Words. Embryonic germ cells • Embryonic stem cells • Human • Pluripotency • Primordial germ cells • Testis
Correspondence: Correspondence: Candace L. Kerr, Ph.D., Institute for Cellular Engineering, Department of Obstetrics and Gynecology, Johns Hopkins University, Broadway Research Building, Suite 771, 733 North Broadway, Baltimore, MD 21205, USA. Telephone: 410-614-3444; Fax: 410-955-7427; e-mail: ckerr{at}jhmi.edu
Received on July 27, 2007;
accepted for publication on November 6, 2007.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS November 15, 2007.
Human primordial germ cells (PGCs) have proven to be a source of pluripotent stem cells called embryonic germ cells (EGCs). However, the developmental potency of these cells in the fetal gonad still remains elusive. Thus, this study provides a comprehensive analysis of pluripotent and germ cell marker expression in human fetal testis 7–15 weeks postfertilization (pF) and compares this expression to their ability to derive EGCs. Although the majority of germ cells expressed stem cell markers stage-specific embryonic antigen (SSEA) 1, SSEA4, EMA-1, and alkaline phosphatase, only a small percentage of those (<1%) expressed OCT4, CKIT, and NANOG. Specifically, the number of OCT4+/CKIT+/NANOG+ cells significantly increased in the developing cords during weeks 7–9, followed by a gradual decline into week 15 pF. By week 15 pF, the remaining OCT4+/CKIT+/NANOG+ cells were found in the cords surrounding the periphery of the testis, and the predominant germ cells, CKIT+ cells, no longer expressed OCT4 or NANOG. Based on morphology and early germ cell marker expression, including VASA, PUM2, and DAZL, we suggest these cells are mitotically active gonocytes or prespermatogonia. Importantly, the number of OCT4+ cells correlated with an increase in the number of EGC colonies derived in culture. Interestingly, two pluripotent markers, Tra-1–60 and Tra-1–81, although highly expressed in EGCs, were not expressed by PGCs in the gonad. Together, these results suggest that PGCs maintain expression of pluripotent stem cell markers during and after sexual differentiation of the gonad, albeit in very low numbers.
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