Cell fate conversion-from the viewpoint of small molecules and lineage specifiers.
Mammalian development was generally considered a naturally unidirectional and irreversible process. However, pioneering work of recent decades has highlighted the plasticity of mammalian cells and implied the possibilities of manipulating cell fate in vitro. Pluripotent stem cells, which hold great potential for regenerative medicine, have been shown to be reprogrammed from differentiated cells either by somatic cell nuclear transfer or by ectopic expression of pluripotency factors. Nevertheless, it remained unknown whether the reprogramming could be accomplished without pluripotency genes. Recent studies show that lineage specifiers play an important role in orchestrating the process of restoring pluripotency by replacing pluripotency-associated transcription factors. Moreover, a combination of small molecules enables the acquisition of pluripotency from somatic cells without any transgenes, offering a tractable platform to precisely dissect the induction and maintenance of cell identity. Here, we will discuss recent scientific advances regarding the cell fate conversion mediated by small molecules or lineage specifiers, especially in the chemically induced somatic cell reprogramming process, and will provide new insights into the intermediate plastic state and "seesaw model" established by chemical approaches during reprogramming.
Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Center for Molecular and Translational Medicine, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.|Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, College of Life Sciences, Peking University, Beijing, China.
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Zhao
Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Center for Molecular and Translational Medicine, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
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Li
Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Center for Molecular and Translational Medicine, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China. hongkui_deng@pku.edu.cn.|Shenzhen Stem Cell Engineering Laboratory, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China. hongkui_deng@pku.edu.cn.
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Deng
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D000066670:Cell Plasticity; D065150:Cellular Reprogramming; D000067470:Cellular Reprogramming Techniques; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D039904:Pluripotent Stem Cells
chemical reprogramming; lineage specifiers; pluripotency; small molecules; “seesaw model”