Our recent derivation of embryonic stem (ES) cell lines from rhesus monkeys, common marmosets, and humans has widespread implications for human developmental biology, drug discovery, drug testing, and transplantation medicine. After months or years of growth in culture dishes, these cells retain the ability to form cells ranging from heart muscle to nerve to blood--potentially any cell type that makes up the body. The proliferative and developmental potential of human ES cells promises an essentially unlimited supply of specific cell types for in vitro experimental studies and for transplantation therapies for diseases such as heart disease, Parkinson's disease, and leukemia. In the long run, however, the greatest legacy for human ES cells may be not as a source of tissue for transplantation medicine, but as a basic research tool to understand the human body. This new tool will be particularly important for lineages that differ significantly between humans and mice. The Exploratory Center for Human Embryonic Stem Cell Research proposed here will begin to focus on using human ES cells to study questions in basic human biology that are not easily addressed by other approaches. A center core will provide human ES cell tissue culture support, including media preparation, quality control, fibroblast preparation, and routine SKY chromosomal analysis of cultured human ES cells. In the final year of funding, a small, focused workshop will be organized to bring together human ES cell researchers and other basic biologists to identify challenges and opportunities in the human ES cell field. We propose the following Pilot Projects: ? ? (I) We will analyze the transciptional changes in one important early lineage: the transition from human ES cell to primitive ectoderm to neural ectoderm to differentiated neurons. (II) We will analyze the transcriptional control of how BMP4 causes human ES cells to exit self-renewal and differentiate to trophoblast, using expression cloning strategies and iRNA to add and subtract function. (III) We will use a biochemical approach, coupled with cutting-edge mass spectrometry and proteomics, to identify those factors produced by fibroblasts that mediate human ES cell self-renewal. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM069981-04
Application #
7116454
Study Section
Special Emphasis Panel (ZGM1-CMB-8 (SC))
Program Officer
Zatz, Marion M
Project Start
2003-09-30
Project End
2007-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
4
Fiscal Year
2006
Total Cost
$731,765
Indirect Cost
Name
Wicell Research Institute
Department
Type
DUNS #
122477024
City
Madison
State
WI
Country
United States
Zip Code
53726
Levenstein, Mark E; Berggren, W Travis; Lee, Ji Eun et al. (2008) Secreted proteoglycans directly mediate human embryonic stem cell-basic fibroblast growth factor 2 interactions critical for proliferation. Stem Cells 26:3099-107
Xu, Ren-He; Sampsell-Barron, Tori L; Gu, Feng et al. (2008) NANOG is a direct target of TGFbeta/activin-mediated SMAD signaling in human ESCs. Cell Stem Cell 3:196-206
Yu, Junying; Vodyanik, Maxim A; Smuga-Otto, Kim et al. (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917-20
Ludwig, Tenneille E; Bergendahl, Veit; Levenstein, Mark E et al. (2006) Feeder-independent culture of human embryonic stem cells. Nat Methods 3:637-46
Levenstein, Mark E; Ludwig, Tenneille E; Xu, Ren-He et al. (2006) Basic fibroblast growth factor support of human embryonic stem cell self-renewal. Stem Cells 24:568-74
Yu, Junying; Vodyanik, Maxim A; He, Ping et al. (2006) Human embryonic stem cells reprogram myeloid precursors following cell-cell fusion. Stem Cells 24:168-76
Xu, Ren-He; Peck, Ruthann M; Li, Dong S et al. (2005) Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells. Nat Methods 2:185-90