Submitted October 25, 2007
Returned for revision November 20, 2007
Accepted January 9, 2008
Gamete Biology
The Early Human Germ Cell Lineage Does Not Express SOX2 During In Vivo Development or Upon In Vitro Culture
Rebecca M. Perrett ,
Lee Turnpenny ,
Judith J. Eckert ,
Marie O'Shea ,
Si Brask Sonne ,
Iain T. Cameron ,
David I. Wilson ,
Ewa Rajpert-De Meyts ,
and
Neil A. Hanley *
* To whom correspondence should be addressed. E-mail: n.a.hanley{at}soton.ac.uk.
Abstract
NANOG, POU5F1 and SOX2 are required by the inner cell mass of the blastocyst and act cooperatively to maintain pluripotency in both mouse and human embryonic stem cells. Inadequacy of any one of them causes loss of the undifferentiated state. Mouse primordial germ cells (PGCs), from which pluripotent embryonic germ cells (EGCs) are derived, also express POU5F1, NANOG and SOX2. Thus, a similar expression profile has been predicted for human PGCs. Here we show by RT-PCR, immunoblotting and immunohistochemistry that human PGCs express POU5F1 and NANOG but not SOX2, with no evidence of redundancy within the Group B family of human SOX genes. Although lacking SOX2, proliferative human germ cells can still be identified in situ during early development and are capable of culture in vitro. Surprisingly, with the exception of FGF4, many stem cell-restricted SOX2 target genes remained detected within the human SOX2-negative germ cell lineage. These studies demonstrate an unexpected difference in gene expression between human and mouse. The human PGC is the first primary cell-type described to express POU5F1 and NANOG but not SOX2. The data also provide a new reference point for studies attempting to turn human stem cells into gametes by normal developmental pathways for the treatment of infertility.
Key words:
Gamete Biology •
Gene regulation •
Human development •
Human stem cell biology •
Primordial germ cells
