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Monitoring Stem Cell Research 
manipulation of the early post-implantation human embryo could 
jeopardize the health of the resulting child, it has never been 
possible to examine this important period of human development 
experimentally. Nearly all of what is knov\m about early human 
development, especially in the early post-implantation period, is 
based on very rare histological sections of human embryos, or on an 
imperfect analogy to experimental studies in the mouse. The mouse 
has been the mainstay of mammalian experimental embryology 
because of its historical use, well-defined genetics, and favorable 
reproductive characteristics. However, early mouse development 
and early human development differ significantly. For example, 
human and mouse embryos differ in the expression of embryonic 
antigens; timing of embryonic genome expression; formation, 
structure, and function of the fetal membranes and placenta; and 
formation of an embryonic disc instead of an egg cylinder. Thus, if 
one is interested in the development of a human tissue known to 
differ significantly from the corresponding mouse tissue, such as the 
yolk sac or the placenta, studying a human model is desirable. 
The first differentiation event in mammalian embryos is the 
formation of the trophectoderm, the outer epithelial layer of the 
blastocyst. The trophectoderm is crucial for implantation of the 
embryo and gives rise to specialized populations of trophoblast cells 
in the placenta [48, 49]. Mouse and human placentas differ in 
structure and function, and these differences are clinically 
significant. For example, the placental hormone chorionic 
gonadotropin, which has an essential role in establishing and 
maintaining human pregnancy, is not even produced by the mouse 
placenta. When formed into chimeras with intact preimplantation 
embryos, mouse ES cells rarely contribute to the trophoblast, and the 
manipulation of external culture conditions has, to date, failed to 
direct mouse ES cells to form trophoblast (50). 
Spontaneously differentiated rhesus monkey [51] or human 
ES cells [1] do secrete modest amounts of chorionic gonadotropin, 
indicating the differentiation of trophoblast cells [52]. Recently it 
was discovered that a single growth factor (BMP4) would induce 
human ES cells to differentiate to a pure population of early 
trophoblast [40]. These early human trophoblast cells have never 
before been available for detailed study, and already this new 
experimental model has provided information about the specific 
genes that control the early development of the human placenta [40]. 
The derivation of other early lineages from human ES cells in vitro to 
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