{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:15:10Z","timestamp":1791512110943,"version":"4.3.4"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T00:00:00Z","timestamp":1574294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"DOI":"10.3389\/fcell.2019.00300","type":"journal-article","created":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T04:19:52Z","timestamp":1574309992000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":51,"title":["One-Carbon Metabolism Regulates Embryonic Stem Cell Fate Through Epigenetic DNA and Histone Modifications: Implications for Transgenerational Metabolic Disorders in Adults"],"prefix":"10.3389","volume":"7","author":[{"given":"Lon J.","family":"Van Winkle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Ryznar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,11,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.cell.2011.03.003","article-title":"Wdr5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network.","volume":"145","author":"Ang","year":"2011","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.semcancer.2019.01.005","article-title":"A regulatory circuitry locking pluripotent stemness to embryonic stem cell: interaction between threonine catabolism and histone methylation.","volume":"57","author":"Chen","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1146\/annurev-animal-020518-115206","article-title":"One-carbon metabolism: linking nutritional biochemistry to epigenetic programming of long-term development.","volume":"7","author":"Clare","year":"2019","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"B4","doi-asserted-by":"crossref","first-page":"958","DOI":"10.18632\/oncoscience.280","article-title":"Activation of the methylation cycle in cells reprogrammed into a stem cell-like state.","volume":"2","author":"Fern\u00e1ndez-Arroyo","year":"2015","journal-title":"Oncoscience"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1842","DOI":"10.1016\/S0140-6736(18)30312-X","article-title":"Origins of lifetime health around the time of conception: causes and consequences.","volume":"391","author":"Fleming","year":"2018","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2016.00017","article-title":"At least three transporters likely mediate threonine uptake needed for mouse embryonic stem cell proliferation.","volume":"4","author":"Formisano","year":"2016","journal-title":"Front. Cell Dev. Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1002\/pros.20089","article-title":"A comprehensive characterization of the peptide and protein constituents of human seminal fluid.","volume":"61","author":"Fung","year":"2004","journal-title":"Prostate"},{"key":"B8","doi-asserted-by":"publisher","first-page":"4337","DOI":"10.1096\/fj.12-210401","article-title":"Pregnancy in aged rats that were born small: cardiorenal and metabolic adaptations and second-generation fetal growth.","volume":"26","author":"Gallo","year":"2012","journal-title":"FASEB J."},{"key":"B9","doi-asserted-by":"publisher","first-page":"619","DOI":"10.4161\/epi.5.7.12882","article-title":"Gestational low protein diet in the rat mediates Igf2 gene expression in male offspring via altered hepatic DNA methylation.","volume":"5","author":"Gong","year":"2010","journal-title":"Epigenetics"},{"key":"B10","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.ydbio.2011.10.021","article-title":"Leucine and arginine regulate trophoblast motility through mTOR-dependent and independent pathways in the preimplantation mouse embryo.","volume":"361","author":"Gonz\u00e1lez","year":"2012","journal-title":"Dev. Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"T105","DOI":"10.1530\/JOE-19-0009","article-title":"Epigenetic responses and the developmental origins of health and disease.","volume":"242","author":"Goyal","year":"2019","journal-title":"J. Endocrinol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"R159","DOI":"10.1530\/REP-18-0431","article-title":"Mitochondria in early development: linking the microenvironment, metabolism and the epigenome.","volume":"157","author":"Harvey","year":"2019","journal-title":"Reproduction"},{"key":"B13","doi-asserted-by":"publisher","first-page":"928","DOI":"10.4161\/epi.6.7.16263","article-title":"Methylation variation at IGF2 differentially methylated regions and maternal folic acid use before and during pregnancy.","volume":"6","author":"Hoyo","year":"2011","journal-title":"Epigenetics"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-319-31143-2_103-1","article-title":"Threonine catabolism: an unexpected epigenetic regulator of mouse embryonic stem cells","author":"Jog","year":"2017","journal-title":"Handbook of Nutrition, Diet, and Epigenetics"},{"key":"B15","doi-asserted-by":"publisher","first-page":"780S","DOI":"10.3945\/an.115.011031","article-title":"Influence of amino acid metabolism on embryonic stem cell function and differentiation.","volume":"7","author":"Kilberg","year":"2016","journal-title":"Adv. Nutr."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/2874283","article-title":"Pluripotent stem cell metabolism and mitochondria: beyond ATP.","volume":"2017","author":"Lees","year":"2017","journal-title":"Stem Cells Int."},{"key":"B17","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/ijo.2010.122","article-title":"Epigenetic changes in early life and future risk of obesity.","volume":"35","author":"Lillycrop","year":"2011","journal-title":"Int. J. Obesity"},{"key":"B18","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/nature08514","article-title":"Human DNA methylomes at base resolution show widespread epigenomic differences.","volume":"462","author":"Lister","year":"2009","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1530\/REP-14-0619","article-title":"Low female birth weight and advanced maternal age programme alterations in next-generation blastocyst development.","volume":"149","author":"Master","year":"2015","journal-title":"Reproduction"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20061342","article-title":"DNA methylation patterns in the early human embryo and the epigenetic\/imprinting problems: a plea for a more careful approach to human assisted reproductive technology (ART).","volume":"20","author":"Menezo","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1530\/REP-09-0281","article-title":"Paternal DNA packaging in spermatozoa: more than the sum of its parts? DNA, histones, protamines and epigenetics.","volume":"139","author":"Miller","year":"2010","journal-title":"Reproduction"},{"key":"B22","doi-asserted-by":"publisher","first-page":"s110","DOI":"10.1017\/S1751731118000526","article-title":"The epic journey of sperm through the female reproductive tract.","volume":"12","author":"Miller","year":"2018","journal-title":"Animal"},{"key":"B23","author":"Najafzadeh","year":"2018","journal-title":"The Role of Amino Acids and the Threonine-SAM Pathway in the Development of Bovine Inner Cell Mass and Pluripotency"},{"key":"B24","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.cell.2013.09.002","article-title":"Mutation in folate metabolism causes epigenetic instability and transgenerational effects on development.","volume":"155","author":"Padmanabhan","year":"2013","journal-title":"Cell"},{"key":"B25","doi-asserted-by":"publisher","first-page":"23667","DOI":"10.1074\/jbc.M110.216283","article-title":"L-threonine regulates G1\/S phase transition of mouse embryonic stem cells via PI3K\/Akt, MAPKs, and mTORC pathways.","volume":"286","author":"Ryu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"B26","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1002\/wsbm.1209","article-title":"Modeling cellular compartmentation in one-carbon metabolism.","volume":"5","author":"Scotti","year":"2013","journal-title":"Wiley Interdiscipl. Rev."},{"key":"B27","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1016\/j.cmet.2014.03.017","article-title":"Methionine metabolism regulates maintenance and differentiation of human pluripotent stem cells.","volume":"19","author":"Shiraki","year":"2014","journal-title":"Cell Metab."},{"key":"B28","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1126\/science.1226603","article-title":"Influence of threonine metabolism on S-adenosylmethionine and histone methylation.","volume":"339","author":"Shyh-Chang","year":"2013","journal-title":"Science"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2017.00089","article-title":"Maternally contributed folate receptor 1 is expressed in ovarian follicles and contributes to preimplantation development.","volume":"5","author":"Strandgaard","year":"2017","journal-title":"Front. Cell Dev. Biol."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-019-1163-0","article-title":"Paternal nongenetic intergenerational transmission of metabolic disease risk.","volume":"19","author":"Su","year":"2019","journal-title":"Curr. Diab. Rep."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1007\/s00018-017-2703-x","article-title":"Epigenetic differences between na\u00efve and primed pluripotent stem cells.","volume":"75","author":"Takahashi","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1017\/S0007114508921747","article-title":"Transmission of raised blood pressure and endothelial dysfunction to the F2 generation induced by maternal protein restriction in the F0, in the absence of dietary challenge in the F1 generation.","volume":"100","author":"Torrens","year":"2008","journal-title":"Br. J. Nutr."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2017.00100","article-title":"Uterine histone secretion likely fosters early embryo development so efforts to mitigate histone cytotoxicity should be cautious.","volume":"5","author":"Van Winkle","year":"2017","journal-title":"Front. Cell Dev. Biol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1095\/biolreprod52.1.96","article-title":"Differences in amino acid content of preimplantation mouse embryos that develop in vitro versus in vivo: in vitro effects of five amino acids that are abundant in oviductal secretions.","volume":"52","author":"Van Winkle","year":"1995","journal-title":"Biol. Reprod."},{"key":"B35","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2014.00018","article-title":"Threonine appears to be essential for proliferation of human as well as mouse embryonic stem cells.","volume":"2","author":"Van Winkle","year":"2014","journal-title":"Front. Cell Dev. Biol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1515\/bmc-2018-0017","article-title":"Can uterine secretion of modified histones alter blastocyst implantation, embryo nutrition, and transgenerational phenotype?","volume":"9","author":"Van Winkle","year":"2018","journal-title":"Biomol. Concepts"},{"key":"B37","author":"Van Winkle","year":"2019","journal-title":"Amino Acid Transporters: Roles for Nutrition, Signalling and Epigenetic Modifications in Embryonic Stem Cells and Their Progenitors."},{"key":"B38","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1093\/humupd\/dmi044","article-title":"System B0,+ amino acid transport regulates the penetration stage of blastocyst implantation with possible long-term developmental consequences through adulthood.","volume":"12","author":"Van Winkle","year":"2006","journal-title":"Hum. Reprod. Update"},{"key":"B39","doi-asserted-by":"crossref","first-page":"T33","DOI":"10.1530\/JOE-18-0676","article-title":"Periconceptional environment and the developmental origins of disease.","volume":"242","author":"Velazquez","year":"2019","journal-title":"J. Endocrinol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1089\/scd.2015.0117","article-title":"Connecting mitochondria, metabolism, and stem cell fate.","volume":"24","author":"Wanet","year":"2015","journal-title":"Stem Cells Dev."},{"key":"B41","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1126\/science.1173288","article-title":"Dependence of mouse embryonic stem cells on threonine catabolism.","volume":"325","author":"Wang","year":"2009","journal-title":"Science"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1038\/ijo.2008.100","article-title":"Methyl donor supplementation prevents transgenerational amplification of obesity.","volume":"32","author":"Waterland","year":"2008","journal-title":"Int. J. Obesity"},{"key":"B43","doi-asserted-by":"publisher","first-page":"10064","DOI":"10.1073\/pnas.1806333115","article-title":"Paternal diet programs offspring health through sperm-and seminal plasma-specific pathways in mice.","volume":"115","author":"Watkins","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/7068567","article-title":"Mitochondrial heterogeneity: evaluating mitochondrial subpopulation dynamics in stem cells.","volume":"2017","author":"Woods","year":"2017","journal-title":"Stem Cells Int."},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/3894101","article-title":"One-carbon metabolism links nutrition intake to embryonic development via epigenetic mechanisms.","volume":"2019","author":"Wu","year":"2019","journal-title":"Stem Cells Int."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fcell.2019.00300\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T16:32:06Z","timestamp":1612456326000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fcell.2019.00300\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,21]]},"references-count":45,"alternative-id":["10.3389\/fcell.2019.00300"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2019.00300","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,21]]},"article-number":"300"}}