Abstract
Although innovative technologies for somatic cell reprogramming and transdifferentiation provide new strategies for the research of translational medicine, including disease modeling, drug screening, artificial organ development, and cell therapy, recipient safety remains a concern due to the use of exogenous transcription factors during induction. To resolve this problem, new induction approaches containing clinically applicable small molecules have been explored. Small molecule epigenetic modulators such as DNA methylation writer inhibitors, histone methylation writer inhibitors, histone acylation reader inhibitors, and histone acetylation eraser inhibitors could overcome epigenetic barriers during cell fate conversion. In the past few years, significant progress has been made in reprogramming and transdifferentiation of somatic cells with small molecule approaches. In the present review, we systematically discuss recent achievements of pure chemical reprogramming and transdifferentiation.
Highlights
In 1958, Gurdon et al first reported unknown factors in the oocyte cytoplasm could reprogram differentiated cells to a pluripotent state [1]
In 1987, Davis et al discovered that a single transcription factor, MyoD, was able to induce fibroblasts directly into myoblasts, which indicated only a few transcription factors could make cell fate decisions [2]
In 2013, Deng’s team reported that mouse fibroblasts could be induced to iPSCs via a combination of seven small molecules (VPA, CHIR99021, RepSox, Tranylcypromine, Forskolin, DZNep, and TTNPB) [18]; this induction method has been challenged by other labs [19]
Summary
In 1958, Gurdon et al first reported unknown factors in the oocyte cytoplasm could reprogram differentiated cells to a pluripotent state [1]. Two research groups independently succeeded in creating human iPSCs using a similar method [4, 5]. With this new iPSC technology, the molecular mechanisms of cell fate transition could be investigated and diverse applications, including drug screening, disease modeling, and cell therapy, could be developed [6]. Chemical compounds similar to those employed to treat human diseases for decades have several unique advantages. Their structural versatility permits modulation of induction time and concentration [12]. Decisions will undoubtedly accelerate the pace of biomedical studies and clinical translation
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