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Small Molecules that Promote Self-Renewal of Stem Cells and Somatic Cell Reprogramming

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Abstract

The ground state of embryonic stem cells (ESCs) is closely related to the development of regenerative medicine. Particularly, long-term culture of ESCs in vitro, maintenance of their undifferentiated state, self-renewal and multi-directional differentiation ability is the premise of ESCs mechanism and application research. Induced pluripotent stem cells (iPSC) reprogrammed from mouse embryonic fibroblasts (MEF) cells into cells with most of the ESC characteristics show promise towards solving ethical problems currently facing stem cell research. However, integration into chromosomal DNA through viral-mediated genes may activate proto oncogenes and lead to risk of cancer of iPSC. At the same time, iPS induction efficiency needs to be further improved to reduce the use of transcription factors. In this review, we discuss small molecules that promote self-renewal and reprogramming, including growth factor receptor inhibitors, GSK-3β and histone deacetylase inhibitors, metabolic regulators, pathway modulators as well as EMT/MET regulation inhibitors to enhance maintenance of ESCs and enable reprogramming. Additionally, we summarize the mechanism of action of small molecules on ESC self-renewal and iPSC reprogramming. Finally, we will report on the progress in identification of novel and potentially effective agents as well as selected strategies that show promise in regenerative medicine. On this basis, development of more small molecule combinations and efficient induction of chemically induced pluripotent stem cell (CiPSC) is vital for stem cell therapy. This will significantly improve research in pathogenesis, individualized drug screening, stem cell transplantation, tissue engineering and many other aspects.

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Abbreviations

ESCs:

Embryonic stem cells

iPSC:

Induced pluripotent stem cells

GSK-3β:

Glycogen synthesis kinase 3β

BIO:

6-bromoindirubin-3′-oxime

MAPK:

Mitogen Activated Protein Kinase

ERK:

Extracellular Regulated protein Kinase

RasGAP:

RasGTP-activated protein

PI3K:

Phosphatidyl inositol-3-kinase

PDK1:

Phosphoinositide-dependent kinase-1

MET:

Mesenchymal cells to epithelial cells

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No.81802960), the Fundamental Research Funds for the Central Universities (No.22120180035), the Shanghai Municipal Population and Family Planning Commission (No.201640346), the National Natural Science Foundation of China (No.81671468), Shanghai Clinical Medicine Field Project of Science and Technology Innovation Action Program (No.17411951600) and Shanghai Municipal Medical and Health Discipline Construction Projects (No.2017ZZ02015).

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  1. Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China

    Guofang Chen, Yu’e Guo & Chao Li

  2. Departments of Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China

    Shuangdi Li

  3. Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China

    Xiaoping Wan

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  1. Guofang Chen
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Chen, G., Guo, Y., Li, C. et al. Small Molecules that Promote Self-Renewal of Stem Cells and Somatic Cell Reprogramming. Stem Cell Rev and Rep 16, 511–523 (2020). https://doi.org/10.1007/s12015-020-09965-w

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