{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T16:04:27Z","timestamp":1779552267097,"version":"3.53.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFA0108200"],"award-info":[{"award-number":["2018YFA0108200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFA0108201"],"award-info":[{"award-number":["2018YFA0108201"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Starting Funding of South China University of Technology","award":["D6201880"],"award-info":[{"award-number":["D6201880"]}]},{"name":"Research Starting Funding of South China University of Technology","award":["K5180910"],"award-info":[{"award-number":["K5180910"]}]},{"name":"Research Starting Funding of South China University of Technology","award":["K5204120"],"award-info":[{"award-number":["K5204120"]}]},{"name":"Research Starting Funding of South China University of Technology","award":["D6212440"],"award-info":[{"award-number":["D6212440"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Human embryonic stem cell (hESC)-derived hepatocytes (hEHs) display functional deficits, particularly impaired albumin secretion and ammonia metabolism, compared to primary human hepatocytes (PHHs). Here, we investigated the regulatory role of CCAAT\/enhancer-binding protein beta (C\/EBP\u03b2) in hepatocyte maturation. Forced C\/EBP\u03b2 expression enhanced hepatocyte functionality and upregulated hepatocyte-specific genes, while suppressing epithelial-mesenchymal transition (EMT) via downregulating canonical EMT markers. Mechanistically, CUT&amp;Tag and luciferase reporter assays confirmed C\/EBP\u03b2 directly bound to the promoter regions of CDH1 (E-cadherin) and CPS1 (carbamoyl phosphate synthetase 1). Co-immunoprecipitation identified an interaction between C\/EBP\u03b2 and the MAPK pathway. RNA interference combined with Western blot analysis revealed that MAPK1-mediated phosphorylation of C\/EBP\u03b2 at Thr-235 augmented its transactivation activity, accelerating hepatocyte maturation. Our findings establish C\/EBP\u03b2 as a master regulator that coordinates transcriptional networks and post-translational modifications during hEHs maturation, providing novel insights for generating mature hepatocytes for disease modeling and regenerative medicine applications.<\/jats:p>","DOI":"10.1093\/stmcls\/sxag016","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T11:31:57Z","timestamp":1774956717000},"source":"Crossref","is-referenced-by-count":0,"title":["Dual roles of MAPK-mediated C\/EBP\u03b2 phosphorylation in promoting maturation and suppressing EMT during hepatocyte differentiation from hESCs"],"prefix":"10.1093","volume":"44","author":[{"given":"Shoupei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, The Second Affiliated Hospital, School of Medicine, South China University of Technology , Guangzhou 510006,","place":["China"]},{"name":"Laboratory of Stem Cells and Translational Medicine, Institute for Clinical Medicine, The Second Affiliated Hospital, School of Medicine, South China University of Technology , Guangzhou 510180,","place":["China"]},{"name":"Laboratory of Stem Cells and Translational Medicine, Institutes for Life Sciences, School of Medicine, South China University of Technology , Guangzhou 510006,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangting","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, The Second Affiliated Hospital, School of Medicine, South China University of Technology , Guangzhou 510006,","place":["China"]},{"name":"Laboratory of Stem Cells and Translational Medicine, Institute for Clinical Medicine, The Second Affiliated Hospital, School of Medicine, South China University of Technology , Guangzhou 510180,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, The Second Affiliated Hospital, School of Medicine, South China University of Technology , Guangzhou 510006,","place":["China"]},{"name":"Laboratory of Stem Cells and Translational Medicine, Institute for Clinical Medicine, The Second Affiliated Hospital, School of Medicine, South China University of Technology , Guangzhou 510180,","place":["China"]},{"name":"Laboratory of Stem Cells and Translational Medicine, Institutes for Life Sciences, School of Medicine, South China University of Technology , Guangzhou 510006,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital , Guangzhou 510180,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, The Second Affiliated Hospital, School of Medicine, South China University of Technology , Guangzhou 510006,","place":["China"]},{"name":"Laboratory of Stem Cells and Translational Medicine, Institute for Clinical Medicine, The Second Affiliated Hospital, School of Medicine, South China University of Technology , Guangzhou 510180,","place":["China"]},{"name":"Laboratory of Stem Cells and Translational Medicine, Institutes for Life Sciences, School of Medicine, South China University of Technology , Guangzhou 510006,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, The Second Affiliated Hospital, School of Medicine, South China University of Technology , Guangzhou 510006,","place":["China"]},{"name":"Laboratory of Stem Cells and Translational Medicine, Institute for Clinical Medicine, The Second Affiliated Hospital, School of Medicine, South China University of Technology , Guangzhou 510180,","place":["China"]},{"name":"Laboratory of Stem Cells and Translational Medicine, Institutes for Life Sciences, School of Medicine, South China University of Technology , Guangzhou 510006,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, The Second Affiliated Hospital, School of Medicine, South China University of Technology , Guangzhou 510006,","place":["China"]},{"name":"Laboratory of Stem Cells and Translational Medicine, Institute for Clinical Medicine, The Second Affiliated Hospital, School of Medicine, South China University of Technology , Guangzhou 510180,","place":["China"]},{"name":"Laboratory of Stem Cells and Translational Medicine, Institutes for Life Sciences, School of Medicine, South China University of Technology , Guangzhou 510006,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weili","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital , Guangzhou 510180,","place":["China"]},{"name":"Surgical Department of Hepatobiliary Pancreas and Spleen, The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University , Guangzhou 510645,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, The Second Affiliated Hospital, School of Medicine, South China University of Technology , Guangzhou 510006,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1402-7402","authenticated-orcid":false,"given":"Yuyou","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, The Second Affiliated Hospital, School of Medicine, South China University of Technology , Guangzhou 510006,","place":["China"]},{"name":"Laboratory of Stem Cells and Translational Medicine, Institute for Clinical Medicine, The Second Affiliated Hospital, School of Medicine, South China University of Technology , Guangzhou 510180,","place":["China"]},{"name":"Laboratory of Stem Cells and Translational Medicine, Institutes for Life Sciences, School of Medicine, South China University of Technology , Guangzhou 510006,","place":["China"]},{"name":"National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology , Guangzhou 510006,","place":["China"]},{"name":"The Innovation Centre of Ministry of Education for Development and Diseases, The Second Affiliated Hospital, School of Medicine, South China University of Technology , Guangzhou 510006,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"2026052311061593900_sxag016-B1","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s41419-020-2259-9","article-title":"Generation of qualified clinical-grade functional hepatocytes from human embryonic stem cells in chemically defined 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