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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Main Authors: Guofang Chen, Shasha Yin, Hongliang Zeng, Haisen Li, Xiaoping Wan
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Life
Subjects:
Online Access:https://www.mdpi.com/2075-1729/12/8/1151
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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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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