The formation and specification of mesoderm results in the generation of a wide range of tissues, including blood, endothelium, heart and skeletal muscle. Many of the known regulatory molecules in these process were identified through the use of model systems such as Xenopus, Zebrafish and the chick embryo that provide access to cell population undergoing mesoderm commitment. The goals of the experiments in this proposal build on preliminary findings which demonstrate that ES cells, engineered to express the green fluorescence protein (GFP) under control of the brachyury locus provide an in vitro model for studying mesoderm induction. With this model, cells expressing the mesoderm gene brachyury can be monitored and/or isolated based on GFP expression. In the first aim of the proposal, we propose to define the kinetics of mesoderm development in this ES model and characterize the full developmental potential of the GFP+ cells.
The second aim will focus on understanding the role of known mesoderm regulators on the development and specification of the ES cell derived GFP+/brachyury+ cells. In the third aim, we will isolate mesoderm subpopulations with different developmental fates and define their molecular differences by Affymetrix microarray analysis. The information from these studies will provide a better understanding of the development of mesoderm-derived cell populations and tissues in the early embryo. This information could ultimately provide insights into Underlying causes of disease of the hematopoietic and cardiovascular system.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Hematology Subcommittee 2 (HEM)
Program Officer
Thomas, John
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Mount Sinai School of Medicine
Internal Medicine/Medicine
Schools of Medicine
New York
United States
Zip Code
Adler, Eric D; Chen, Vincent C; Bystrup, Anne et al. (2010) The cardiomyocyte lineage is critical for optimization of stem cell therapy in a mouse model of myocardial infarction. FASEB J 24:1073-81
Cheng, Xin; Huber, Tara L; Chen, Vincent C et al. (2008) Numb mediates the interaction between Wnt and Notch to modulate primitive erythropoietic specification from the hemangioblast. Development 135:3447-58
Chen, Vincent C; Stull, Robert; Joo, Daniel et al. (2008) Notch signaling respecifies the hemangioblast to a cardiac fate. Nat Biotechnol 26:1169-78
Kattman, Steven J; Adler, Eric D; Keller, Gordon M (2007) Specification of multipotential cardiovascular progenitor cells during embryonic stem cell differentiation and embryonic development. Trends Cardiovasc Med 17:240-6
Vigneau, Cecile; Polgar, Katalin; Striker, Gary et al. (2007) Mouse embryonic stem cell-derived embryoid bodies generate progenitors that integrate long term into renal proximal tubules in vivo. J Am Soc Nephrol 18:1709-20
Kattman, Steven J; Huber, Tara L; Keller, Gordon M (2006) Multipotent flk-1+ cardiovascular progenitor cells give rise to the cardiomyocyte, endothelial, and vascular smooth muscle lineages. Dev Cell 11:723-32
Kubo, Atsushi; Chen, Vincent; Kennedy, Marion et al. (2005) The homeobox gene HEX regulates proliferation and differentiation of hemangioblasts and endothelial cells during ES cell differentiation. Blood 105:4590-7
D'Souza, Sunita L; Elefanty, Andrew G; Keller, Gordon (2005) SCL/Tal-1 is essential for hematopoietic commitment of the hemangioblast but not for its development. Blood 105:3862-70
Kouskoff, Valerie; Lacaud, Georges; Schwantz, Staci et al. (2005) Sequential development of hematopoietic and cardiac mesoderm during embryonic stem cell differentiation. Proc Natl Acad Sci U S A 102:13170-5
Kubo, Atsushi; Shinozaki, Katsunori; Shannon, John M et al. (2004) Development of definitive endoderm from embryonic stem cells in culture. Development 131:1651-62