Regulation of Embryonic Stem Cell Self-Renewal
Embryonic stem cells (ESCs) are a type of cells capable of self-renewal and multi-directional differentiation. The self-renewal of ESCs is regulated by factors including signaling pathway proteins, transcription factors, epigenetic regulators, cytokines, and small molecular compounds. Similarly, non...
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MDPI AG
2022-07-01
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author | Guofang Chen Shasha Yin Hongliang Zeng Haisen Li Xiaoping Wan |
author_facet | Guofang Chen Shasha Yin Hongliang Zeng Haisen Li Xiaoping Wan |
author_sort | Guofang Chen |
collection | DOAJ |
description | Embryonic stem cells (ESCs) are a type of cells capable of self-renewal and multi-directional differentiation. The self-renewal of ESCs is regulated by factors including signaling pathway proteins, transcription factors, epigenetic regulators, cytokines, and small molecular compounds. Similarly, non-coding RNAs, small RNAs, and microRNAs (miRNAs) also play an important role in the process. Functionally, the core transcription factors interact with helper transcription factors to activate the expression of genes that contribute to maintaining pluripotency, while suppressing the expression of differentiation-related genes. Additionally, cytokines such as leukemia suppressor factor (LIF) stimulate downstream signaling pathways and promote self-renewal of ESCs. Particularly, LIF binds to its receptor (LIFR/gp130) to trigger the downstream Jak-Stat3 signaling pathway. BMP4 activates the downstream pathway and acts in combination with Jak-Stat3 to promote pluripotency of ESCs in the absence of serum. In addition, activation of the Wnt-FDZ signaling pathway has been observed to facilitate the self-renewal of ESCs. Small molecule modulator proteins of the pathway mentioned above are widely used in in vitro culture of stem cells. Multiple epigenetic regulators are involved in the maintenance of ESCs self-renewal, making the epigenetic status of ESCs a crucial factor in this process. Similarly, non-coding RNAs and cellular energetics have been described to promote the maintenance of the ESC’s self-renewal. These factors regulate the self-renewal and differentiation of ESCs by forming signaling networks. This review focused on the role of major transcription factors, signaling pathways, small molecular compounds, epigenetic regulators, non-coding RNAs, and cellular energetics in ESC’s self-renewal. |
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last_indexed | 2024-03-09T04:13:31Z |
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spelling | doaj.art-e6d4f305b55e45c297b0389eab4c011e2023-12-03T13:58:35ZengMDPI AGLife2075-17292022-07-01128115110.3390/life12081151Regulation of Embryonic Stem Cell Self-RenewalGuofang Chen0Shasha Yin1Hongliang Zeng2Haisen Li3Xiaoping Wan4Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, ChinaShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, ChinaInstitute of Chinese Materia Medica, Hunan Academy of Chinese Medicine, Changsha 410013, ChinaSchool of Medicine, Wayne State University, Detroit, MI 48201, USAShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, ChinaEmbryonic stem cells (ESCs) are a type of cells capable of self-renewal and multi-directional differentiation. The self-renewal of ESCs is regulated by factors including signaling pathway proteins, transcription factors, epigenetic regulators, cytokines, and small molecular compounds. Similarly, non-coding RNAs, small RNAs, and microRNAs (miRNAs) also play an important role in the process. Functionally, the core transcription factors interact with helper transcription factors to activate the expression of genes that contribute to maintaining pluripotency, while suppressing the expression of differentiation-related genes. Additionally, cytokines such as leukemia suppressor factor (LIF) stimulate downstream signaling pathways and promote self-renewal of ESCs. Particularly, LIF binds to its receptor (LIFR/gp130) to trigger the downstream Jak-Stat3 signaling pathway. BMP4 activates the downstream pathway and acts in combination with Jak-Stat3 to promote pluripotency of ESCs in the absence of serum. In addition, activation of the Wnt-FDZ signaling pathway has been observed to facilitate the self-renewal of ESCs. Small molecule modulator proteins of the pathway mentioned above are widely used in in vitro culture of stem cells. Multiple epigenetic regulators are involved in the maintenance of ESCs self-renewal, making the epigenetic status of ESCs a crucial factor in this process. Similarly, non-coding RNAs and cellular energetics have been described to promote the maintenance of the ESC’s self-renewal. These factors regulate the self-renewal and differentiation of ESCs by forming signaling networks. This review focused on the role of major transcription factors, signaling pathways, small molecular compounds, epigenetic regulators, non-coding RNAs, and cellular energetics in ESC’s self-renewal.https://www.mdpi.com/2075-1729/12/8/1151embryonic stem cells (ESCs)self-renewaltranscription factorssignaling pathwayssmall molecular compoundsepigenetics |
spellingShingle | Guofang Chen Shasha Yin Hongliang Zeng Haisen Li Xiaoping Wan Regulation of Embryonic Stem Cell Self-Renewal Life embryonic stem cells (ESCs) self-renewal transcription factors signaling pathways small molecular compounds epigenetics |
title | Regulation of Embryonic Stem Cell Self-Renewal |
title_full | Regulation of Embryonic Stem Cell Self-Renewal |
title_fullStr | Regulation of Embryonic Stem Cell Self-Renewal |
title_full_unstemmed | Regulation of Embryonic Stem Cell Self-Renewal |
title_short | Regulation of Embryonic Stem Cell Self-Renewal |
title_sort | regulation of embryonic stem cell self renewal |
topic | embryonic stem cells (ESCs) self-renewal transcription factors signaling pathways small molecular compounds epigenetics |
url | https://www.mdpi.com/2075-1729/12/8/1151 |
work_keys_str_mv | AT guofangchen regulationofembryonicstemcellselfrenewal AT shashayin regulationofembryonicstemcellselfrenewal AT hongliangzeng regulationofembryonicstemcellselfrenewal AT haisenli regulationofembryonicstemcellselfrenewal AT xiaopingwan regulationofembryonicstemcellselfrenewal |