{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T07:18:43Z","timestamp":1780730323202,"version":"3.54.1"},"reference-count":59,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32060232"],"award-info":[{"award-number":["32060232"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20212BAB206075"],"award-info":[{"award-number":["20212BAB206075"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The differentiation of mesenchymal stem cells (MSCs) into hepatocyte\u2010like cells (HLCs) is considered one of the most promising strategies for alternative hepatocyte transplantation to treat end\u2010stage liver disease. To advance this method, it is crucial to gain a deeper understanding of the mechanisms governing hepatogenic differentiation. The study demonstrated that suppression of the intracellular domain release of the Notch pathway receptor via the \u03b3\u2010secretase inhibitor N\u2010[(3, 5\u2010difluorophenyl)acetyl]\u2010L\u2010alanyl\u20102\u2010phenylglycine\u20101, 1\u2010dimethylethyl ester (DAPT) significantly promotes the expression of hepatocyte\u2010related genes and proteins in HLCs. Increased expression of intracellular inducible NO synthase (iNOS) during differentiation led to elevated endogenous NO production. Biotin switch assays revealed a gradual increase in S\u2010nitrosylation (SNO)\u2010NOTCH1 and a decrease in overall NOTCH1 expression during hepatogenic differentiation. The addition of the exogenous NO donor S\u2010nitrosoglutathione (GSNO) and the SNO inhibitor dithiothreitol (DTT) further demonstrated that the elevated expression of SNO\u2010NOTCH1 promotes the differentiation of MSCs into mature hepatocytes. Briefly, our results fully demonstrated that the modification of the extracellular domain of NOTCH1 by NO, leading to the formation of SNO\u2010NOTCH1, significantly promotes hepatogenic differentiation by inhibiting the Notch signalling pathway. Our study highlights the critical role of SNO\u2010NOTCH1 in regulating the Notch signalling pathway and offers new insights into the mechanisms driving this differentiation process.<\/jats:p>","DOI":"10.1111\/jcmm.70274","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T17:16:43Z","timestamp":1733851003000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["S\u2010Nitrosylation of <scp>NOTCH1<\/scp> Regulates Mesenchymal Stem Cells Differentiation Into Hepatocyte\u2010Like Cells by Inhibiting Notch Signalling Pathway"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1816-4981","authenticated-orcid":false,"given":"Xuesong","family":"Wang","sequence":"first","affiliation":[{"name":"Subcenter for Stem Cell Clinical Translation First Affiliated Hospital of Gannan Medical University  Ganzhou Jiangxi China"},{"name":"School of Rehabilitation Medicine Gannan Medical University  Ganzhou Jiangxi China"},{"name":"Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine  Ganzhou Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Subcenter for Stem Cell Clinical Translation First Affiliated Hospital of Gannan Medical University  Ganzhou Jiangxi China"},{"name":"School of Rehabilitation Medicine Gannan Medical University  Ganzhou Jiangxi China"},{"name":"Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine  Ganzhou Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Subcenter for Stem Cell Clinical Translation First Affiliated Hospital of Gannan Medical University  Ganzhou Jiangxi China"},{"name":"College of Nursing, Gannan Medical University  Ganzhou Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingkun","family":"Tang","sequence":"additional","affiliation":[{"name":"Subcenter for Stem Cell Clinical Translation First Affiliated Hospital of Gannan Medical University  Ganzhou Jiangxi China"},{"name":"School of Rehabilitation Medicine Gannan Medical University  Ganzhou Jiangxi China"},{"name":"Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine  Ganzhou Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Subcenter for Stem Cell Clinical Translation First Affiliated Hospital of Gannan Medical University  Ganzhou Jiangxi China"},{"name":"School of Rehabilitation Medicine Gannan Medical University  Ganzhou Jiangxi China"},{"name":"Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine  Ganzhou Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenming","family":"Lu","sequence":"additional","affiliation":[{"name":"Subcenter for Stem Cell Clinical Translation First Affiliated Hospital of Gannan Medical University  Ganzhou Jiangxi China"},{"name":"School of Rehabilitation Medicine Gannan Medical University  Ganzhou Jiangxi China"},{"name":"Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine  Ganzhou Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Chen","sequence":"additional","affiliation":[{"name":"Subcenter for Stem Cell Clinical Translation First Affiliated Hospital of Gannan Medical University  Ganzhou Jiangxi China"},{"name":"School of Rehabilitation Medicine Gannan Medical University  Ganzhou Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lincai","family":"Li","sequence":"additional","affiliation":[{"name":"Subcenter for Stem Cell Clinical Translation First Affiliated Hospital of Gannan Medical University  Ganzhou Jiangxi China"},{"name":"Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine  Ganzhou Jiangxi China"},{"name":"Jiangxi Provincial Key Laboratory of Tissue Engineering Gannan Medical University  Ganzhou Jiangxi China"},{"name":"Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases Ministry of Education, Gannan Medical University  Ganzhou Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Subcenter for Stem Cell Clinical Translation First Affiliated Hospital of Gannan Medical University  Ganzhou Jiangxi China"},{"name":"Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine  Ganzhou Jiangxi China"},{"name":"Jiangxi Provincial Key Laboratory of Tissue Engineering Gannan Medical University  Ganzhou Jiangxi China"},{"name":"Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases Ministry of Education, Gannan Medical University  Ganzhou Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4336-1933","authenticated-orcid":false,"given":"Junsong","family":"Ye","sequence":"additional","affiliation":[{"name":"Subcenter for Stem Cell Clinical Translation First Affiliated Hospital of Gannan Medical University  Ganzhou Jiangxi China"},{"name":"Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine  Ganzhou Jiangxi China"},{"name":"Jiangxi Provincial Key Laboratory of Tissue Engineering Gannan Medical University  Ganzhou Jiangxi China"},{"name":"Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases Ministry of Education, Gannan Medical University  Ganzhou Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1361084"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2024.05.020"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2024.04.015"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/4654912"},{"issue":"1","key":"e_1_2_13_6_1","first-page":"11","article-title":"Amniotic Mesenchymal Stem Cells Derived Hepatocyte\u2010Like Cells Attenuated Liver Fibrosis More Efficiently by Mixed\u2010Cell Transplantation","volume":"12","author":"Wang H.","year":"2020","journal-title":"International Journal of Physiology, Pathophysiology and Pharmacology"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.2485\/jhtb.29.215"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.111672"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v13.i10.1580"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1217211"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2512-2"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-07633-7"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2012.09.008"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-023-03276-w"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37949-0"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-024-01208-z"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molp.2020.05.013"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2013.04.001"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe3706"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/8404168"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/03008207.2019.1611792"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/14653240600855905"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/09636897231210069"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.227124"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/35055104"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2023.0003"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.02.015"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.10.072"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840080619"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2024.03.021"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-015-0085-2"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-020-05884-8"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.408"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep25594"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/stcltm\/szad076"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13060547"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2009.05.007"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2764"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.10.016"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-023-03370-z"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v13.i10.1580"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/burnst\/tkad032"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-08379-y"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2017.224"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2024.116655"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2015.05.001"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220185110"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI73780"},{"issue":"17","key":"e_1_2_13_49_1","article-title":"3D Printing of a Vascularized Mini\u2010Liver Based on the Size\u2010Dependent Functional Enhancements of Cell Spheroids for Rescue of Liver Failure","volume":"11","author":"Zhang J.","year":"2024","journal-title":"Advancement of Science"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.2174\/1574888X18666230125113254"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-015-0180-2"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v12.i15.2394"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.12.024"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10116"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/stcltm\/szae030"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-021-00139-x"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.111006"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plantsci.2013.10.014"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.066404"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.11.009"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.70274","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T10:17:47Z","timestamp":1735208267000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.70274"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":59,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/jcmm.70274"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.70274","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12]]},"assertion":[{"value":"2024-08-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70274"}}