Transdifferentiation by defined factors as a powerful research tool to address basic biological questions

Abstract

Ectopic expression of master regulators can change the fate of a given cell and convert it to a different cell type. This has been demonstrated by the conversion of fibroblasts into several cell types, such as embryonic stem cells (ESCs), neurons, hepatocytes and cardiomyocytes, that could function properly in their native environment. Recently, we demonstrated the conversion of fibroblasts into embryonic Sertoli-like cells (ieSCs) by ectopic expression of five factors. These cells harbor many of the characteristics of the endogenous cells and could incorporate into testicular cords and support the survival of germ cells and neurons in culture. It is clear today that transdifferentiated cells provide a new impetus in the field of regenerative medicine. Here we will discuss whether transdifferentiation could also be used as a research tool to illuminate basic developmental processes in animals. There are several traditional approaches to identify regulators of biological processes. These include analysis of candidate genes in transgenic/knockout mice, computational analyses followed by in vitro loss/gain-of-function experiments and high-throughput screen using random mutagenic agent or shRNA libraries. However, not all cell types can be sustained in culture, and there are many genes that cause early lethality and therefore are difficult to be explored in vivo. Moreover, a systematic approach to uncover the most pivotal regulators of a given process is still missing. During reprogramming, each factor either alone or in combination with the other factors contributes to the conversion by initiating a unique process that controls Transdifferentiation by defined factors as a powerful research tool to address basic biological questions

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