February 5, 2015
During development, cells make decisions that direct their fate from an unspecified state toward a mature cell type. This requires coordination of highly orchestrated changes in gene expression that define how a cell transitions into a very specialized cell niche. My work focuses on mechanisms that underlie commitment of two cell types that form from a common origin but generate completely different mature fates, namely heart (cardiomyocyte) and blood vessel (endothelial) cells. The goal of this seminar is to discuss mesoderm patterning and how lineage biases and barriers emerge from very early stages of development that define cell identity during formation of the cardiovascular system. I will begin by discussing general background on mesoderm fate specification from gastrulation to formation of a mature cardiovascular system. I will then discuss the use of human pluripotent stem cells as a model system and analytical methods for studying early stages of human development. Using this background, I will discuss two vignettes that show how cells can co-opt an alternate identity during cardiovascular development. 1) I will discuss the role of a transmembrane protein (TMEM88) required for specification of the heart and loss of this molecule converts cells to a blood vessel fate and 2) I will discuss how manipulation of a key signaling pathway is sufficient to convert a blood vessel cell into a heart muscle cell. I will close with a perspective on why it is important to study mechanisms of cell fate commitment with implications for basic sciences and translational therapeutics.