During embryonic development, differentiation of embryonic stem cells (ESCs) results in a loss of lineage potential as cells become more committed and functionally restricted. This process was always thought to be unidirectional. However, the discovery that somatic cells could be reprogrammed back to a pluripotent state (induced pluripotent stem cells, or iPSCs) after the transduction of four defined transcription factors forever altered our initially restricted view of cellular plasticity (Takahashi and Yamanaka, 2006). With this discovery came a number of possibilities, and a number of questions. Our reprogramming research focuses on answering the following fundamental questions though a variety of approaches:
How does a cell revert back to a pluripotent state?
Our laboratory is building a number of screening tools, so that multiple genes, proteins, miRNAs, or chemicals of interest can be assessed for their function in reprogramming, enabling us to strategically assess the mechanistic significance of key pathways.
How malleable and universal is reprogramming?
We are exploring new reprogramming methodologies and somatic sources, to obtain safe, efficient and practical approaches for iPSC generation, as this is a critical step for any future clinical use of iPSCs.
What are the consequences, if any, following these cellular conversions?
We are working to understand how the genome/epigenome changes during reprogramming, and if any of the changes that occur are influenced by the reprogramming methodology or somatic source utilized.
Are the reprogrammed cellular products functionally identical to their normal counterparts?
Importantly, we also seek to understand if any of the genetic/epigenetic aberrancies that exist in iPSCs are of functional significance, by determining if they are either necessary for the reprogramming process, can influence iPSC-directed differentiation potential, or can affect the function of the resultant cell lineages.
Answers to these questions are critical steps towards understanding the mechanisms governing reprogramming, and for harnessing the full potential of this breakthrough technology.