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First published online December 28, 2004
doi: 10.1242/10.1242/dev.01586

Development 132, 227-233 (2005)
Published by The Company of Biologists 2005
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A germ cell origin of embryonic stem cells?

Thomas P. Zwaka1 and James A. Thomson1,2,*

1 University of Wisconsin - Medical School and The National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA
2 WiCell Research Institute, Madison, WI 53715, USA



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  		Fig. 1. Early development of the mouse embryo. (A) Six days after fertilization (E6.25), the mouse embryo consists of three layers. The inner cell mass (ICM) cells that are in contact with the blastocyst cavity differentiate into an epithelial layer called the extra-embryonic (primitive) endoderm. The rest of the ICM becomes the epiblast (primitive ectoderm). Primordial germ cells (PGCs, red dots) arise from a cell population in the proximal epiblast adjacent to the extra-embryonic ectoderm. These cells then pass through the primitive streak and give rise to several extra-embryonic mesodermal lineages and to germ cells. (B) By E7.25, a distinct cluster of ~45 tissue non-specific, alkaline phosphatase (Tnap)-positive PGCs is present at the base of the allantois within the extra-embryonic mesoderm (red dots). Once these PGCs are specified, they begin to migrate to the future gonadal anlagen. A, anterior; P, posterior; Pr, proximal; D, distal.

 


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  		Fig. 2. Germ cell propagation in vitro and in vivo. (A-C) The germ cell cycle in the mouse. (A) Primordial germ cells (PGCs) appear at E7.25 as a small group of cells (red) in the extra-embryonic mesoderm. (B) After E8.5, PGCs start to migrate to the gonadal anlagen and contribute (C) during puberty to oocytes or sperm. (D) Embryonic stem (ES) cells are in vitro derivatives of inner cell mass (ICM) cells. (E,F) The formation of ES cells occurs either directly from the ICM/primitive ectoderm (E) or according to our hypothesis, through in vitro differentiation of ICM outgrowth into primitive ectoderm, then into extra-embryonic mesoderm and finally into PGCs (F). (G) PGCs that form in vivo (A-C) give rise to embryonic germ (EG) cells in vitro. Germ cells, PGCs, ES and EG cells are all capable of forming teratomas and teratocarcinomas. ES and EG cells can reintegrate into the normal embryo after injection into the blastocyst (not shown). Circular green arrows denote unlimited self-renewal.

 




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