overexpressed in the fetal yolk sac. The hematopoi- 
etic microenvironment in the fetal yolk sac is also 
being studied, using cell lines generated from me- 
soderm tissue in which hematopoiesis is known to 
originate. 
III. Gene Transfer and Targeting in Embryonic Stem 
Cells. 
Embryonic stem (ES) cells are totipotent cells de- 
rived from day 3.5 murine blastocysts. Such cells 
can be manipulated in vitro and reintroduced into 
embryos by microinjection. The introduced cells 
contribute to somatic and germline chimerism and 
thus can be used to generate transgenic mice. Ho- 
mologous recombination methods can be used to 
PUBLICATIONS 
target specific sequences in the ES cells for disrup- 
tion. Dr. Williams's laboratory is using ES cells for 
generation of transgenic mice to study fetal hema- 
topoiesis. In addition, ES cells are being used to 
study the effect of lineage-specific expression of the 
growth -regulating proto-oncogene, c-Myc. A long- 
term goal is the generation of murine models of 
human diseases, using gene targeting methods in 
ES cells. 
Dr. Williams is also Assistant Professor of Pediat- 
rics, Harvard Medical School, and Associate in He- 
matology-Oncology, Children's Hospital, Boston, 
and Clinical Associate at the Dana-Farber Cancer 
Institute. 
Article 
Williams, D.A., Rosenblatt, M.F., Beier, D.R., and Cone, R.D. 1988. Generation of murine stromal cell lines 
supporting hematopoietic stem cell proliferation by use of recombinant retrovirus vectors encoding sim- 
ian virus 40 large T antigen. Mol Cell Biol 8:5864-5871. 
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