Reprogramming with Small Molecules instead of Exogenous Transcription Factors.

Tongxiang Lin,Shouhai Wu

doi:10.1155/2015/794632

Abstract

Induced pluripotent stem cells (iPSCs) could be employed in the creation of patient-specific stem cells, which could subsequently be used in various basic and clinical applications. However, current iPSC methodologies present significant hidden risks with respect to genetic mutations and abnormal expression which are a barrier in realizing the full potential of iPSCs. A chemical approach is thought to be a promising strategy for safety and efficiency of iPSC generation. Many small molecules have been identified that can be used in place of exogenous transcription factors and significantly improve iPSC reprogramming efficiency and quality. Recent studies have shown that the use of small molecules results in the generation of chemically induced pluripotent stem cells from mouse embryonic fibroblast cells. These studies might lead to new areas of stem cell research and medical applications, not only human iPSC by chemicals alone, but also safe generation of somatic stem cells for cell based clinical trials and other researches. In this paper, we have reviewed the recent advances in small molecule approaches for the generation of iPSCs.

Highlights

Human induced pluripotent stem cells are similar to human embryonic stem cells in that they have the potential to differentiate into cells of all three germ layers [1–3]
Adult cells were induced into induced pluripotent stem cells (iPSCs) through exogenous overexpression of the transcription factors Oct4, Sox2, cMyc, and Klf4
Huangfu et al studied the compound application in iPSC generation; they investigated the effects of the histone deacetylase (HDAC) inhibitor valproic acid (VPA) and found that reprogramming efficiency was increased 100-fold over that of the transcription factor method [31]

Summary

Introduction

Human induced pluripotent stem cells (iPSCs) are similar to human embryonic stem cells in that they have the potential to differentiate into cells of all three germ layers [1–3]. Adult cells were induced into iPSCs through exogenous overexpression of the transcription factors Oct ( known as Pou5f1), Sox, cMyc, and Klf. Adult cells were induced into iPSCs through exogenous overexpression of the transcription factors Oct ( known as Pou5f1), Sox, cMyc, and Klf4 Efficiency of this technique is at very low level, with around 0.1% of mouse fibroblasts [4] and 0.01% of human fibroblasts cell [2, 5]. The human iPSC by using chemicals only has not been developed yet, human stem cells studied with small molecules are revealing further details about epigenetic remodeling Hopefully these researches might relieve concerns about the specificity, efficiency, kinetics, and safety of generating human iPSCs and bring human iPSC closer. We provide perspective views of the possibility of the iPSC generation from human somatic cells and its future applications

Compounds That May Improve the Reprogramming Efficiency and Quality

Compounds That Can Replace Reprogramming Factors

Findings

Conclusions and Perspectives