Pluripotency and Differentiation in Normal and Cancer Stem Cells

Embryonic stem cells and induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type under the correct conditions. These cells have allowed for the development of novel research tools, opened new avenues for therapy and given birth to the field of regenerative medicine. One of the key features of iPS cells is their epigenome, which is distinct from that of differentiated cells (all cell types have the same complement of genes). The distinct chromatin structure of pluripotent cells, along with a complement of stem cell-specific transcription factors, drives their unique transcription profiles and phenotypic characteristics. To realize the therapeutic potential of iPSC, advances in how to control and direct epigenetic changes are required so that differentiated cell types can be generated efficiently and specifically. The research team in the Epigenetic Etiology of Human Disease Lab is analyzing DNA methylation and histone modifications over the stem cell genome and during their stepwise differentiation to specific cell lineages.

Additional studies in the laboratory examine how normal stem cells differ from their transformed counterparts, known as cancer stem cells or cancer-initiating cells. For this study, the brain tumor glioma is used as a model since there is good evidence for a cancer stem cell-driven component in this tumor. As part of these studies, we examine epigenetic signatures before and after differentiation of glioma and normal neural stem cells to pinpoint cancer stem cell-specific epigenetic abnormalities.

To realize the potential of stem cell therapies, an understanding of how to generate pure populations of differentiated cell types is crucial, and the epigenome is key to this regulation. The study of cancer stem cells is expected to produce a better understanding of how these cells originate; how they contribute to tumor initiation, promotion and treatment resistance; and how they can be specifically targeted by novel treatments such as differentiation therapy.