Detailed lines of work > Differentiation of embryonic stem cells

  • Video: Rhythmic beating of cardiomyocites differentiated from human ES cells.

The availability of human embryonic stem (ES) cell lines has provided new avenues for understanding human early embryogenesis and organogenesis, as well as for developing genuinely human experimental models of disease.

Furthermore, human ES cells hold great potential for cell replacement therapies.

Human ES cells differentiate in vitro and in vivo into derivatives of the three embryo lineages: endoderm, ectoderm, and mesoderm. Thus, at least theoretically, human ES cells could be used to generate specialized cells that are missing or damaged in a particular disease. However, our understanding of the mechanisms that regulate human ES cell differentiation into specific cell types is very limited.

The problem of differentiating human ES cells into specific cell types has been mainly addressed from an empirical standpoint. Even though several protocols exist that favor ES cell differentiation toward specific cell lineages, there is currently no example of a defined factor or mixture of factors that promote specific differentiation of human (or mouse) ES cells into any particular cell type.

Our laboratory is actively seeking methods to drive ES cell differentiation into specialized cells, including cardiomyocytes, chondrocytes, and blood progenitor cells.

For this purpose, we are using a threefold approach. In hypothesis-driven experiments, we are trying to reproduce the normal developmental steps of lineage commitment and differentiation in human ES cells in vitro. In parallel, we are using microarray analyses to characterize global changes in gene expression associated to the spontaneous differentiation of human ES cells toward the cell types of interest. In a complementary approach, we intend to use high-content assays to evaluate the effect of small molecules and nearly genome-wide gene over-expression or downregulation on the differentiation of human ES cells to specific cell types.

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