The Role of Epigenetic Modifications in Stem Cell Pluripotency and Differentiation

  • Image shows how understanding epigenetic changes that regulate cellular differentiation is key to developing stem cell therapies for patients.

  • This is a model for the role of epigenetic changes in the generation of tumor-initiating cells in human cancers.

Embryonic stem cells and induced pluripotent stem cells have the capacity to differentiate into any cell type under the correct conditions, creating potential for improving human health. The key to these cells is their epigenome, which is distinct from differentiated cells in human tissues. In fact, the epigenome and the associated gene expression profile are the only difference between stem cells and their differentiated progeny; their DNA sequences are identical. To realize this potential, advances in how to control and direct epigenetic changes are required so that differentiated cell types can be generated efficiently and specifically.

The team is analyzing DNA methylation and a panel of histone modifications over the stem cell genome and during their stepwise differentiation to specific cell lineages. Additional studies examine how normal stem cells differ from their transformed counterparts, cancer stem cells or cancer initiating cells. Glioma is used as a model to study epigenetic and transcriptional differences between normal and transformed stem cells.

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 for novel treatments such as differentiation therapy.