Nuclear reprogramming in cell–free extracts

Abstract

Methods for directly turning a somatic cell type into another type (a process referred to as transdifferentiation) would be beneficial for producing replacement cells for therapeutic applications. Adult stem cells have been shown to display a broader differentiation potential than anticipated and may contribute to tissues other than those in which they reside. In addition, novel transdifferentiation strategies are being developed. I report recent results on the functional reprogramming of a somatic cell using a nuclear and cytoplasmic extract derived from another somatic cell type. The reprogramming of 293T fibroblasts in an extract from T cells is evidenced by nuclear uptake and the assembly of transcription factors, induction of activity of a chromatin remodelling complex, changes in chromatin composition and activation of lymphoid cell–specific genes. The reprogrammed cells express T–cell–specific surface molecules and a complex regulatory function. Reprogramming cells in cell–free extracts may create possibilities for producing replacement cells for therapeutic applications. The system may also constitute a powerful tool to examine the mechanisms of nuclear reprogramming, at least as they occurin vitro.