{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:58:05Z","timestamp":1791050285622,"version":"4.1.0"},"reference-count":64,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["Z01 ES102205"],"award-info":[{"award-number":["Z01 ES102205"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31730110 and 31661143031"],"award-info":[{"award-number":["31730110 and 31661143031"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA230631 and R01DK111430"],"award-info":[{"award-number":["R01CA230631 and R01DK111430"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2020M681437"],"award-info":[{"award-number":["2020M681437"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Sphingolipids are important structural components of cell membranes and prominent signaling molecules controlling cell growth, differentiation, and apoptosis. Sphingolipids are particularly abundant in the brain, and defects in sphingolipid degradation are associated with several human neurodegenerative diseases. However, molecular mechanisms governing sphingolipid metabolism remain unclear. Here, we report that sphingolipid degradation is under transcriptional control of SIRT1, a highly conserved mammalian NAD\n                    <jats:sup>+<\/jats:sup>\n                    -dependent protein deacetylase, in mouse embryonic stem cells (mESCs). Deletion of SIRT1 results in accumulation of sphingomyelin in mESCs, primarily due to reduction of SMPDL3B, a GPI-anchored plasma membrane bound sphingomyelin phosphodiesterase. Mechanistically, SIRT1 regulates transcription of\n                    <jats:italic>Smpdl3b<\/jats:italic>\n                    through c-Myc. Functionally, SIRT1 deficiency-induced accumulation of sphingomyelin increases membrane fluidity and impairs neural differentiation in vitro and in vivo. Our findings discover a key regulatory mechanism for sphingolipid homeostasis and neural differentiation, further imply that pharmacological manipulation of SIRT1-mediated sphingomyelin degradation might be beneficial for treatment of human neurological diseases.\n                  <\/jats:p>","DOI":"10.7554\/elife.67452","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T08:00:40Z","timestamp":1622102440000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.67452","source":"Crossref","is-referenced-by-count":38,"title":["SIRT1 regulates sphingolipid metabolism and neural differentiation of mouse embryonic stem cells through c-Myc-SMPDL3B"],"prefix":"10.7554","volume":"10","author":[{"given":"Wei","family":"Fan","sequence":"first","affiliation":[{"name":"Signal Transduction Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, Triangle Park, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Tang","sequence":"additional","affiliation":[{"name":"Signal Transduction Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, Triangle Park, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Fan","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Fang","sequence":"additional","affiliation":[{"name":"Signal Transduction Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, Triangle Park, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, Research Triangle Park, Triangle Park, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leping","family":"Li","sequence":"additional","affiliation":[{"name":"Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Triangle Park, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1988-7337","authenticated-orcid":true,"given":"Jian","family":"Xu","sequence":"additional","affiliation":[{"name":"Children's Medical Center Research Institute, Department of Pediatrics, Harold C. 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