{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:40:15Z","timestamp":1792183215034,"version":"4.4.0"},"reference-count":24,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6116","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.sciencemag.org\/site\/feature\/contribinfo\/prep\/license.xhtml"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["4R00CA168997-02"],"award-info":[{"award-number":["4R00CA168997-02"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RC2HL102815"],"award-info":[{"award-number":["RC2HL102815"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 HL100001"],"award-info":[{"award-number":["U01 HL100001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM56203"],"award-info":[{"award-number":["R01 GM56203"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2013,1,11]]},"abstract":"<jats:title>SAM, Histones, and Stem Cells<\/jats:title>\n                  <jats:p>\n                    Mouse embryonic stem cells require threonine for growth and express large amounts of the enzyme that catalyzes the first step in threonine metabolism. To find out what is so important about threonine in these cells,\n                    <jats:bold>\n                      Shyh-Change\n                      <jats:italic>et al.<\/jats:italic>\n                    <\/jats:bold>\n                    (p.\n                    <jats:related-article xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" page=\"222\" related-article-type=\"in-this-issue\" vol=\"339\" xlink:href=\"10.1126\/science.1226603\">222<\/jats:related-article>\n                    , published online 1 November; see the Perspective by\n                    <jats:related-article xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" issue=\"6116\" page=\"148\" related-article-type=\"in-this-issue\" vol=\"339\" xlink:href=\"10.1126\/science.1233423\">\n                      <jats:bold>Sassone-Corsi<\/jats:bold>\n                    <\/jats:related-article>\n                    ) monitored changes in metabolism by mass spectrometry in induced pluripotent stem cells. Threonine was required to maintain cellular concentrations of S-adenosylmethionine (SAM), a substrate used for protein methylation. Restriction of threonine inhibited methylation of histones, which is characteristic of chromatin in embryonic stem cells. Thus, altered metabolism of threonine and methionine in stem cells may be linked to epigenetic changes that influence genetic reprogramming and decisions of stem cells to proliferate or differentiate.\n                  <\/jats:p>","DOI":"10.1126\/science.1226603","type":"journal-article","created":{"date-parts":[[2012,11,2]],"date-time":"2012-11-02T02:51:03Z","timestamp":1351824663000},"page":"222-226","source":"Crossref","is-referenced-by-count":616,"title":["Influence of Threonine Metabolism on\n                    <i>S<\/i>\n                    -Adenosylmethionine and Histone Methylation"],"prefix":"10.1126","volume":"339","author":[{"given":"Ng","family":"Shyh-Chang","sequence":"first","affiliation":[{"name":"Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital and Dana-Farber Cancer Institute, Boston, MA 02115, USA."},{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Harvard Stem Cell Institute, Cambridge, MA 02138, USA."},{"name":"Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Department of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason W.","family":"Locasale","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."},{"name":"Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costas A.","family":"Lyssiotis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."},{"name":"Department of Systems 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Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital and Dana-Farber Cancer Institute, Boston, MA 02115, USA."},{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Harvard Stem Cell Institute, Cambridge, MA 02138, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juli J.","family":"Unternaehrer","sequence":"additional","affiliation":[{"name":"Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital and Dana-Farber Cancer Institute, Boston, MA 02115, USA."},{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Harvard Stem Cell Institute, Cambridge, MA 02138, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital and Dana-Farber Cancer Institute, Boston, MA 02115, USA."},{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Harvard Stem Cell Institute, Cambridge, MA 02138, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Asara","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George Q.","family":"Daley","sequence":"additional","affiliation":[{"name":"Stem Cell Transplantation Program, Division of Pediatric 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