{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:35:31Z","timestamp":1792805731325,"version":"4.5.0"},"reference-count":159,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Natural Science Foundation of Shanghai by Guofang Chen","award":["22ZR1449100"],"award-info":[{"award-number":["22ZR1449100"]}]},{"name":"the Natural Science Foundation of Shanghai by Guofang Chen","award":["81902874"],"award-info":[{"award-number":["81902874"]}]},{"name":"the National Natural Science Foundation of China by Shasha Yin","award":["22ZR1449100"],"award-info":[{"award-number":["22ZR1449100"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"the National Natural Science Foundation of China by Shasha Yin","award":["81902874"],"award-info":[{"award-number":["81902874"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>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\u2019s 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\u2019s self-renewal.<\/jats:p>","DOI":"10.3390\/life12081151","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T02:06:42Z","timestamp":1659319602000},"page":"1151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Regulation of Embryonic Stem Cell Self-Renewal"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4250-1682","authenticated-orcid":false,"given":"Guofang","family":"Chen","sequence":"first","affiliation":[{"name":"Shanghai 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Yin","sequence":"additional","affiliation":[{"name":"Shanghai 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongliang","family":"Zeng","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, Hunan Academy of Chinese Medicine, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haisen","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Wan","sequence":"additional","affiliation":[{"name":"Shanghai 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7634","DOI":"10.1073\/pnas.78.12.7634","article-title":"Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells","volume":"78","author":"Martin","year":"1981","journal-title":"Proc. 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