{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T19:53:55Z","timestamp":1792439635442,"version":"4.5.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["rep.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Somatic cell nuclear transfer (SCNT) has been successfully used for cloning in a variety of mammalian species. However, SCNT reprogramming efficiency is relatively low, in part, due to incomplete DNA methylation reprogramming of donor cell nuclei. We previously showed that ten-eleven translocation 3 (TET3) is responsible for active DNA demethylation during preimplantation embryonic development in bovines. In this study, we constructed TET3-overexpressing cell lines in vitro and observed that the use of these fibroblasts as donor cells increased the blastocyst rate by approximately 18 percentage points compared to SCNT. The overexpression of TET3 in bovine SCNT embryos caused a decrease in the global DNA methylation level of the pluripotency genes Nanog and Oct-4, ultimately resulting in an increase in the transcriptional activity of these pluripotency genes. Moreover, the quality of bovine TET3-NT embryos at the blastocyst stage was significantly improved, and bovine TET3-NT blastocysts possessed more total number of cells and fewer apoptotic cells than the SCNT blastocysts, similar to in vitro fertilization (IVF) embryos. Nevertheless, DNA methylation of the imprinting control region (ICR) for the imprinted genes H19-IGF2 in SCNT embryos remained unaffected by TET3 overexpression, maintaining parent-specific activity for further development. Thus, the results of our study provide a promising approach to rectify incomplete epigenetic reprogramming and achieve higher cloning efficiency.<\/jats:p>","DOI":"10.1530\/rep-20-0021","type":"journal-article","created":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T13:27:58Z","timestamp":1592314078000},"page":"379-391","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":21,"title":["<i>TET3<\/i>\n                    overexpression facilitates DNA reprogramming and early development of bovine SCNT embryos"],"prefix":"10.1093","volume":"160","author":[{"given":"Jian","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine , Jilin University, Changchun, Jilin, China"},{"name":"Department of Biology , Southern University of Science and Technology, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy , Second Hospital, Jilin University, Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Heat Disease , Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Academy of Translational Medicine , First Hospital, Jilin University, Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Cheng","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine , Jilin University, Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhui","family":"Zhai","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine , Jilin University, Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine , Jilin University, Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinglan","family":"An","sequence":"additional","affiliation":[{"name":"Academy of Translational Medicine , First Hospital, Jilin University, Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Li","sequence":"additional","affiliation":[{"name":"Academy of Translational Medicine , First Hospital, Jilin University, Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueming","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine , Jilin University, Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine , Jilin University, Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,1]]},"reference":[{"key":"2026010712234932600_bib1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1477-7827-3-7","article-title":"Expression of plasminogen activators in preimplantation rat embryos developed in vivo and in vitro","volume":"3","author":"Aflalo","year":"2005","journal-title":"Reproductive Biology and Endocrinology"},{"key":"2026010712234932600_bib2","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/ncb3296","article-title":"De novo DNA methylation drives 5hmC accumulation in mouse zygotes","volume":"18","author":"Amouroux","year":"2016","journal-title":"Nature Cell Biology"},{"key":"2026010712234932600_bib3","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.anireprosci.2006.07.002","article-title":"A review on reproductive biotechnologies for conservation of endangered mammalian species","volume":"99","author":"Andrabi","year":"2007","journal-title":"Animal Reproduction Science"},{"key":"2026010712234932600_bib4","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1634\/stemcells.2005-0350","article-title":"Epigenetic modification is central to genome reprogramming in somatic cell nuclear transfer","volume":"24","author":"Armstrong","year":"2006","journal-title":"Stem Cells"},{"key":"2026010712234932600_bib5","doi-asserted-by":"publisher","first-page":"4067","DOI":"10.1093\/bioinformatics\/bti652","article-title":"BiQ Analyzer: visualization and quality control for DNA methylation data from bisulfite sequencing","volume":"21","author":"Bock","year":"2005","journal-title":"Bioinformatics"},{"issue":"Supplement 1","key":"2026010712234932600_bib6","doi-asserted-by":"publisher","first-page":"S214","DOI":"10.1016\/j.theriogenology.2007.05.059","article-title":"Somatic cell nuclear transfer: past, present and future perspectives","volume":"68","author":"Campbell","year":"2007","journal-title":"Theriogenology"},{"key":"2026010712234932600_bib7","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.theriogenology.2013.10.025","article-title":"Dynamic reprogramming of 5-hydroxymethylcytosine during early porcine embryogenesis","volume":"81","author":"Cao","year":"2014","journal-title":"Theriogenology"},{"key":"2026010712234932600_bib8","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1002\/mrd.23105","article-title":"Tet3 is required for normal in vitro fertilization preimplantation embryos development of bovine","volume":"86","author":"Cheng","year":"2019","journal-title":"Molecular Reproduction and Development"},{"key":"2026010712234932600_bib9","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1016\/j.stem.2015.10.001","article-title":"Histone demethylase expression enhances human somatic cell nuclear transfer efficiency and promotes derivation of pluripotent stem cells","volume":"17","author":"Chung","year":"2015","journal-title":"Cell Stem Cell"},{"key":"2026010712234932600_bib10","doi-asserted-by":"publisher","first-page":"13734","DOI":"10.1073\/pnas.241522698","article-title":"Conservation of methylation reprogramming in mammalian development: aberrant reprogramming in cloned embryos","volume":"98","author":"Dean","year":"2001","journal-title":"PNAS"},{"key":"2026010712234932600_bib11","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1095\/biolreprod.104.033225","article-title":"Methylation and acetylation characteristics of cloned bovine embryos from donor cells treated with 5-aza-2\u2032-deoxycytidine","volume":"72","author":"Enright","year":"2005","journal-title":"Biology of Reproduction"},{"key":"2026010712234932600_bib13","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.stem.2013.02.005","article-title":"Replacement of Oct4 by Tet1 during iPSC induction reveals an important role of DNA methylation and hydroxymethylation in reprogramming","volume":"12","author":"Gao","year":"2013","journal-title":"Cell Stem Cell"},{"key":"2026010712234932600_bib12","doi-asserted-by":"publisher","first-page":"426.e5","DOI":"10.1016\/j.stem.2018.07.017","article-title":"Inhibition of aberrant DNA Re-methylation improves post-implantation development of somatic cell nuclear transfer embryos","volume":"23","author":"Gao","year":"2018","journal-title":"Cell Stem Cell"},{"key":"2026010712234932600_bib14","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1089\/cell.2012.0055","article-title":"Effects of donor fibroblasts expressing OCT4 on bovine embryos generated by somatic cell nuclear transfer","volume":"15","author":"Goissis","year":"2013","journal-title":"Cell Reprogram"},{"issue":"Supplement 6","key":"2026010712234932600_bib15","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1111\/rda.12027","article-title":"Scriptaid and 5-aza-2\u2032deoxycytidine enhanced expression of pluripotent genes and in vitro developmental competence in interspecies black-footed cat cloned embryos","volume":"47","author":"Gomez","year":"2012","journal-title":"Reproduction in Domestic Animals"},{"key":"2026010712234932600_bib16","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/nature10443","article-title":"The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes","volume":"477","author":"Gu","year":"2011","journal-title":"Nature"},{"key":"2026010712234932600_bib17","first-page":"622","article-title":"The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles","volume":"10","author":"Gurdon","year":"1962","journal-title":"Journal of Embryology and Experimental Morphology"},{"key":"2026010712234932600_bib18","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1126\/science.1210944","article-title":"Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA","volume":"333","author":"He","year":"2011","journal-title":"Science"},{"key":"2026010712234932600_bib19","doi-asserted-by":"publisher","first-page":"135.e6","DOI":"10.1016\/j.stem.2017.03.003","article-title":"H3K4 methylation-dependent memory of somatic cell identity inhibits reprogramming and development of nuclear transfer embryos","volume":"21","author":"Hormanseder","year":"2017","journal-title":"Cell Stem Cell"},{"key":"2026010712234932600_bib20","doi-asserted-by":"publisher","first-page":"3642","DOI":"10.1073\/pnas.1014033108","article-title":"Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine","volume":"108","author":"Iqbal","year":"2011","journal-title":"PNAS"},{"key":"2026010712234932600_bib21","doi-asserted-by":"publisher","first-page":"16010","DOI":"10.1038\/celldisc.2016.10","article-title":"Identification of key factors conquering developmental arrest of somatic cell cloned embryos by combining embryo biopsy and single-cell sequencing","volume":"2","author":"Liu","year":"2016","journal-title":"Cell Discovery"},{"key":"2026010712234932600_bib22","doi-asserted-by":"publisher","first-page":"dev158261","DOI":"10.1242\/dev.158261","article-title":"H3K9 demethylase KDM4E is an epigenetic regulator for bovine embryonic development and a defective factor for nuclear reprogramming","volume":"145","author":"Liu","year":"2018","journal-title":"Development"},{"key":"2026010712234932600_bib23","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(T)(-Delta Delta C) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"2026010712234932600_bib24","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1101\/gad.248005.114","article-title":"Role of Tet proteins in enhancer activity and telomere elongation","volume":"28","author":"Lu","year":"2014","journal-title":"Genes and Development"},{"key":"2026010712234932600_bib25","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.stem.2018.06.018","article-title":"Somatic cell nuclear transfer reprogramming: mechanisms and applications","volume":"23","author":"Matoba","year":"2018","journal-title":"Cell Stem Cell"},{"key":"2026010712234932600_bib26","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1093\/hmg\/ddt495","article-title":"RNA sequencing-based identification of aberrant imprinting in cloned mice","volume":"23","author":"Okae","year":"2014","journal-title":"Human Molecular Genetics"},{"key":"2026010712234932600_bib27","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1038\/ng.2393","article-title":"Incomplete methylation reprogramming in SCNT embryos","volume":"44","author":"Peat","year":"2012","journal-title":"Nature Genetics"},{"key":"2026010712234932600_bib28","doi-asserted-by":"publisher","first-page":"76","DOI":"10.4238\/vol8-1gmr541","article-title":"Imprinted gene expression in in vivo- and in vitro-produced bovine embryos and chorio-allantoic membranes","volume":"8","author":"Perecin","year":"2009","journal-title":"Genetics and Molecular Research"},{"key":"2026010712234932600_bib29","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1016\/s0960-9822(03)00419-6","article-title":"Epigenetic marking correlates with developmental potential in cloned bovine preimplantation embryos","volume":"13","author":"Santos","year":"2003","journal-title":"Current Biology"},{"key":"2026010712234932600_bib30","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.stem.2014.09.002","article-title":"Tet3 and DNA replication mediate demethylation of both the maternal and paternal genomes in mouse zygotes","volume":"15","author":"Shen","year":"2014","journal-title":"Cell Stem Cell"},{"key":"2026010712234932600_bib31","doi-asserted-by":"publisher","first-page":"3167","DOI":"10.1016\/j.celrep.2016.08.066","article-title":"Parent-of-origin DNA methylation dynamics during mouse development","volume":"16","author":"Stelzer","year":"2016","journal-title":"Cell Reports"},{"key":"2026010712234932600_bib32","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/1471-213X-9-9","article-title":"In vitro culture and somatic cell nuclear transfer affect imprinting of SNRPN gene in pre- and post-implantation stages of development in cattle","volume":"9","author":"Suzuki","year":"2009","journal-title":"BMC Developmental Biology"},{"key":"2026010712234932600_bib33","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1530\/REP-08-0299","article-title":"The histone deacetylase inhibitor scriptaid enhances nascent mRNA production and rescues full-term development in cloned inbred mice","volume":"138","author":"Van Thuan","year":"2009","journal-title":"Reproduction"},{"key":"2026010712234932600_bib34","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1095\/biolreprod.107.063149","article-title":"Dynamic reprogramming of histone acetylation and methylation in the first cell cycle of cloned mouse embryos","volume":"77","author":"Wang","year":"2007","journal-title":"Biology of Reproduction"},{"key":"2026010712234932600_bib35","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1111\/j.1439-0531.2011.01778.x","article-title":"Histone deacetylase 1 down-regulation on developmental capability and histone acetylation in bovine oocytes and parthenogenetic embryos","volume":"46","author":"Wang","year":"2011","journal-title":"Reproduction in Domestic Animals"},{"key":"2026010712234932600_bib36","doi-asserted-by":"publisher","first-page":"e20154","DOI":"10.1371\/journal.pone.0020154","article-title":"Unfaithful maintenance of methylation imprints due to loss of maternal nuclear Dnmt1 during somatic cell nuclear transfer","volume":"6","author":"Wei","year":"2011","journal-title":"PLoS ONE"},{"key":"2026010712234932600_bib37","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1038\/385810a0","article-title":"Viable offspring derived from fetal and adult mammalian cells","volume":"385","author":"Wilmut","year":"1997","journal-title":"Nature"},{"key":"2026010712234932600_bib38","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/ncomms1240","article-title":"5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming","volume":"2","author":"Wossidlo","year":"2011","journal-title":"Nature Communications"},{"key":"2026010712234932600_bib39","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/ng1973","article-title":"Nuclear reprogramming of cloned embryos and its implications for therapeutic cloning","volume":"39","author":"Yang","year":"2007","journal-title":"Nature Genetics"},{"key":"2026010712234932600_bib40","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/84769","article-title":"Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture","volume":"27","author":"Young","year":"2001","journal-title":"Nature Genetics"},{"key":"2026010712234932600_bib42","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1002\/ar.21457","article-title":"Overexpression Nanog activates pluripotent genes in porcine fetal fibroblasts and nuclear transfer embryos","volume":"294","author":"Zhang","year":"2011","journal-title":"Anatomical Record"},{"key":"2026010712234932600_bib43","doi-asserted-by":"publisher","first-page":"30345","DOI":"10.1038\/srep30345","article-title":"Aberrant DNA methylation reprogramming in bovine SCNT preimplantation embryos","volume":"6","author":"Zhang","year":"2016","journal-title":"Scientific Reports"},{"key":"2026010712234932600_bib41","doi-asserted-by":"publisher","first-page":"e0189542","DOI":"10.1371\/journal.pone.0189542","article-title":"Effect of TET inhibitor on bovine parthenogenetic embryo development","volume":"12","author":"Zhang","year":"2017","journal-title":"PLoS ONE"},{"key":"2026010712234932600_bib44","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1159\/000487579","article-title":"Down-regulation of H3K4me3 by MM-102 facilitates epigenetic reprogramming of porcine somatic cell nuclear transfer embryos","volume":"45","author":"Zhang","year":"2018","journal-title":"Cellular Physiology and Biochemistry"},{"key":"2026010712234932600_bib45","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s41588-017-0007-6","article-title":"Single-cell DNA methylome sequencing of human preimplantation embryos","volume":"50","author":"Zhu","year":"2018","journal-title":"Nature Genetics"}],"container-title":["Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rep.bioscientifica.com\/view\/journals\/rep\/160\/3\/REP-20-0021.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/rep.bioscientifica.com\/downloadpdf\/journals\/rep\/160\/3\/REP-20-0021.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/reproduction\/article-pdf\/160\/3\/379\/64126978\/rep-20-0021.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/reproduction\/article-pdf\/160\/3\/379\/64126978\/rep-20-0021.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T17:23:52Z","timestamp":1767806632000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/reproduction\/article\/160\/3\/379\/8235583"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,1]]},"references-count":45,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,9,1]]}},"URL":"https:\/\/doi.org\/10.1530\/rep-20-0021","relation":{},"ISSN":["1470-1626","1741-7899"],"issn-type":[{"value":"1470-1626","type":"print"},{"value":"1741-7899","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,9,1]]},"published":{"date-parts":[[2020,9,1]]}}}