Bioengineering of Direct Cellular Reprogramming

Transdifferentiation, or direct cell reprogramming, where differentiated cells are reprogrammed into another lineage without going through an intermediate stem cell-like stage, produces cells promising for regenerative medicine. It obviates the use of embryos and minimizes the risk of teratoma formation associated with the use of induced pluripotent stem cells. To facilitate eventual translation of transdifferentiation technologies we focus on developing nonviral have demonstrated the feasibility of converting fibroblasts into neurons by nonviral overexpression of transcription factors. The poor conversion efficiency of nonviral direct cell reprogramming requires improvement. I will discuss our effort on optimizing the biochemical and physical cues to enhance neuronal transdifferentiation. In particular, I will highlight the role of topographical substrates in modulating the purity, conversion kinetics, and subtypes of the induced neurons generated by direct reprogramming. I will also discuss our recent effort on using CRISPR/dCas9 gene activation approach to achieve direct cellular reprogramming.