{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:31:10Z","timestamp":1791412270309,"version":"4.3.3"},"reference-count":52,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2012,6,1]],"date-time":"2012-06-01T00:00:00Z","timestamp":1338508800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2012,6,1]],"date-time":"2012-06-01T00:00:00Z","timestamp":1338508800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["bmn.com","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Current Opinion in Genetics & Development"],"published-print":{"date-parts":[[2012,6]]},"DOI":"10.1016\/j.gde.2012.03.001","type":"journal-article","created":{"date-parts":[[2012,3,29]],"date-time":"2012-03-29T20:05:09Z","timestamp":1333051509000},"page":"272-282","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":87,"title":["Accessing na\u00efve human pluripotency"],"prefix":"10.1016","volume":"22","author":[{"given":"Alejandro","family":"De Los Angeles","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuin-Han","family":"Loh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J","family":"Tesar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George Q","family":"Daley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.gde.2012.03.001_bib0005","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/292154a0","article-title":"Establishment in culture of pluripotential cells from mouse embryos","volume":"292","author":"Evans","year":"1981","journal-title":"Nature"},{"key":"10.1016\/j.gde.2012.03.001_bib0010","doi-asserted-by":"crossref","first-page":"7634","DOI":"10.1073\/pnas.78.12.7634","article-title":"Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells","volume":"78","author":"Martin","year":"1981","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.gde.2012.03.001_bib0015","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.stem.2009.05.015","article-title":"Na\u00efve and primed pluripotent states","volume":"4","author":"Nichols","year":"2009","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0020","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/nature05972","article-title":"New cell lines from mouse epiblast share defining features with human embryonic stem cells","volume":"488","author":"Tesar","year":"2007","journal-title":"Nature"},{"key":"10.1016\/j.gde.2012.03.001_bib0025","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/nature05950","article-title":"Derivation of pluripotent epiblast stem cells from mammalian embryos","volume":"448","author":"Brons","year":"2007","journal-title":"Nature"},{"key":"10.1016\/j.gde.2012.03.001_bib0030","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1126\/science.1092727","article-title":"Epigenetic dynamics of imprinted X inactivation during early mouse development","volume":"303","author":"Okamoto","year":"2003","journal-title":"Science"},{"key":"10.1016\/j.gde.2012.03.001_bib0035_1","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/nature09872","article-title":"Eutherian mammals use diverse strategies to initiate X-chromosome inactivation during development","volume":"472","author":"Okamoto","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.gde.2012.03.001_bib0040_1","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.stem.2011.01.016","article-title":"Isolation of epiblast stem cells from preimplantation mouse embryos","volume":"8","author":"Najm","year":"2011","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0045","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1126\/science.282.5391.1145","article-title":"Embryonic stem cell lines derived from human blastocysts","volume":"282","author":"Thomson","year":"1998","journal-title":"Science"},{"key":"10.1016\/j.gde.2012.03.001_bib0050","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1634\/stemcells.22-5-770","article-title":"LIF\/STAT3 signaling fails to maintain self-renewal of human embryonic stem cells","volume":"22","author":"Daheron","year":"2004","journal-title":"Stem Cells"},{"key":"10.1016\/j.gde.2012.03.001_bib0055","doi-asserted-by":"crossref","first-page":"4495","DOI":"10.1242\/jcs.02553","article-title":"Activin\/Nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells","volume":"118","author":"Vallier","year":"2005","journal-title":"J Cell Sci"},{"key":"10.1016\/j.gde.2012.03.001_bib0060_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.stem.2010.01.003","article-title":"Conserved and divergent roles of FGF signaling in mouse epiblast stem cells and human embryonic stem cells","volume":"5","author":"Greber","year":"2010","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0065_1","doi-asserted-by":"crossref","first-page":"4874","DOI":"10.1038\/emboj.2011.407","article-title":"FGF signaling inhibits neural induction in human embryonic stem cells","volume":"30","author":"Greber","year":"2011","journal-title":"EMBO J"},{"key":"10.1016\/j.gde.2012.03.001_bib0070","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1038\/nbt761","article-title":"BMP4 initiates human embryonic stem cell differentiation to trophoblast","volume":"20","author":"Xu","year":"2002","journal-title":"Nat Biotechnol"},{"key":"10.1016\/j.gde.2012.03.001_bib0075","doi-asserted-by":"crossref","first-page":"e6082","DOI":"10.1371\/journal.pone.0006082","article-title":"Early decisions of human embryonic stem cells and mouse epiblast stem cells are controlled by the same signaling pathways","volume":"4","author":"Vallier","year":"2009","journal-title":"PLoS ONE"},{"key":"10.1016\/j.gde.2012.03.001_bib0080_1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cell.2011.12.007","article-title":"Generation of chimeric rhesus monkeys","volume":"148","author":"Tachibana","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0085","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.cell.2008.01.039","article-title":"Stem cells and early lineage development","volume":"132","author":"Rossant","year":"2008","journal-title":"Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0090","first-page":"235","article-title":"Reflections on the biology of embryonic stem cells","volume":"41","author":"Gardner","year":"1997","journal-title":"Int J Dev Biol"},{"key":"10.1016\/j.gde.2012.03.001_bib0095","doi-asserted-by":"crossref","first-page":"9112","DOI":"10.1158\/0008-5472.CAN-09-3342","article-title":"Genetic factors on mouse chromosome 18 affecting susceptibility to testicular germ cell tumors and permissiveness to embryonic stem cell derivation","volume":"69","author":"Anderson","year":"2009","journal-title":"Cancer Res"},{"key":"10.1016\/j.gde.2012.03.001_bib0100","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nature06968","article-title":"The ground state of embryonic stem cell self-renewal","volume":"453","author":"Ying","year":"2008","journal-title":"Nature"},{"key":"10.1016\/j.gde.2012.03.001_bib0105","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.cell.2008.12.007","article-title":"Capture of authentic embryonic stem cells from rat blastocysts","volume":"135","author":"Buehr","year":"2008","journal-title":"Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0110","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/j.cell.2008.12.006","article-title":"Germline competent embryonic stem cells derived from rat blastocysts","volume":"135","author":"Li","year":"2008","journal-title":"Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0115_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/nature09368","article-title":"Production of p53 gene knockout rats by homologous recombination","volume":"467","author":"Tong","year":"2010","journal-title":"Nature"},{"key":"10.1016\/j.gde.2012.03.001_bib0120_1","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1016\/j.cub.2011.09.010","article-title":"Blimp1 expression predicts embryonic stem cell development in vitro","volume":"21","author":"Chu","year":"2011","journal-title":"Curr Biol"},{"key":"10.1016\/j.gde.2012.03.001_bib0125","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1242\/dev.038893","article-title":"Suppression of Erk signaling promotes ground state pluripotency in the mouse","volume":"136","author":"Nichols","year":"2009","journal-title":"Development"},{"key":"10.1016\/j.gde.2012.03.001_bib0130_1","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.ydbio.2011.10.030","article-title":"Human hypoblast formation is not dependent on FGF signaling","volume":"361","author":"Roode","year":"2012","journal-title":"Dev Biol"},{"key":"10.1016\/j.gde.2012.03.001_bib0135_1","doi-asserted-by":"crossref","DOI":"10.1038\/nature10807","article-title":"Control of ground-state pluripotency by allelic regulation of Nanog","author":"Miyanari","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.gde.2012.03.001_bib0140_1","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.cell.2010.04.010","article-title":"Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations","volume":"141","author":"Lengner","year":"2010","journal-title":"Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0145","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1242\/dev.071688","article-title":"The roles of FGF and MAPK signalingin the segregation of the epiblast and hypoblast lineages in bovine and human embryos","volume":"139","author":"Kuijk","year":"2012","journal-title":"Development"},{"key":"10.1016\/j.gde.2012.03.001_bib0150","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0155","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1126\/science.1151526","article-title":"Induced pluripotent stem cells derived from human somatic cells","volume":"318","author":"Yu","year":"2007","journal-title":"Science"},{"key":"10.1016\/j.gde.2012.03.001_bib0160","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of pluripotent stem cells from mouse embryonic andadult fibroblast cultures by defined factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0165_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/ncb2136","article-title":"Direct reprogramming of fibroblasts into epiblast stem cells","volume":"13","author":"Han","year":"2011","journal-title":"Nat Cell Biol"},{"key":"10.1016\/j.gde.2012.03.001_bib0170","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.stem.2008.11.014","article-title":"Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors","volume":"4","author":"Li","year":"2009","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0175","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.stem.2011.06.004","article-title":"Unexpected X chromosome skewing during culture and reprogramming of human somatic cells can be alleviated using telomerase","volume":"9","author":"Pomp","year":"2011","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0180","doi-asserted-by":"crossref","first-page":"9222","DOI":"10.1073\/pnas.1004584107","article-title":"Human embryonic stem cells with biological and epigenetic characteristics similar to mouse ESCs","volume":"107","author":"Hanna","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.gde.2012.03.001_bib0185","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.stem.2008.08.014","article-title":"A drug-inducible system for direct reprogramming of human somatic cells","volume":"3","author":"Hockemeyer","year":"2008","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0190","article-title":"Human and mouse induced pluripotent stem cells are differentially reprogrammed in response to kinase inhibitors","author":"Hirano","year":"2011","journal-title":"Stem Cells Dev"},{"key":"10.1016\/j.gde.2012.03.001_bib0195","doi-asserted-by":"crossref","first-page":"8299","DOI":"10.1073\/pnas.1014041108","article-title":"Rapid induction and long-term self-renewal of primitive neural precursors from human embryonic stem cells by small molecule inhibitors","volume":"108","author":"Li","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.gde.2012.03.001_bib0200","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.stem.2010.05.003","article-title":"A murine ESC-like state facilitates transgenesis and homologous recombination in human pluripotent stem cells","volume":"6","author":"Buecker","year":"2010","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0205","doi-asserted-by":"crossref","first-page":"18283","DOI":"10.1073\/pnas.1100893108","article-title":"Rapid and efficient reprogramming of somatic cells to induced pluripotent stem cells by retinoic acid receptor gamma and liver receptor homolog 1","volume":"108","author":"Wang","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.gde.2012.03.001_bib0210","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1242\/dev.030957","article-title":"Klf4 reverts developmentally programmed restriction of ground state pluripotency","volume":"136","author":"Guo","year":"2009","journal-title":"Development"},{"key":"10.1016\/j.gde.2012.03.001_bib0215","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.cell.2009.07.039","article-title":"Nanog is the gateway to the pluripotent ground state","volume":"138","author":"Silva","year":"2009","journal-title":"Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0220","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.stem.2009.11.003","article-title":"Oct4 and LIF\/Stat3 additively induce Kruppel factors to sustain embryonic stem cell self-renewal","volume":"5","author":"Hall","year":"2009","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0225","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.stem.2010.06.022","article-title":"Stat3 activation is limiting for reprogramming to ground state pluripotency","volume":"7","author":"Yang","year":"2010","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0230","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1242\/dev.052753","article-title":"A genome-wide screen in EpiSCs identifies Nr5a nuclear receptors as potent inducers of ground state pluripotency","volume":"137","author":"Guo","year":"2010","journal-title":"Development"},{"key":"10.1016\/j.gde.2012.03.001_bib0235","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.stem.2009.04.015","article-title":"Metastable pluripotent states in NOD-mouse derived ESCs","volume":"4","author":"Hanna","year":"2009","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0240","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1038\/nature08534","article-title":"Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells","volume":"461","author":"Bao","year":"2009","journal-title":"Nature"},{"key":"10.1016\/j.gde.2012.03.001_bib0245","doi-asserted-by":"crossref","first-page":"8912","DOI":"10.1073\/pnas.0903860106","article-title":"Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4","volume":"106","author":"Lyssiotis","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.gde.2012.03.001_bib0250","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.stem.2009.03.001","article-title":"Histone deacetylase inhibition elicits an evolutionarily conserved self-renewal program in embryonic stem cells","volume":"4","author":"Ware","year":"2009","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.gde.2012.03.001_bib0255","doi-asserted-by":"crossref","first-page":"4820","DOI":"10.1073\/pnas.0712136105","article-title":"X-chromosome inactivation and epigenetic fluidity in human embryonic stem cells","volume":"105","author":"Silva","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.gde.2012.03.001_bib0260_1","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.cell.2010.10.015","article-title":"Epiblast stem cell subpopulations represent mouse embryos of distinct pregastrulation stages","volume":"143","author":"Han","year":"2010","journal-title":"Cell"}],"container-title":["Current Opinion in Genetics & Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0959437X12000251?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0959437X12000251?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T11:40:38Z","timestamp":1760701238000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0959437X12000251"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,6]]},"references-count":52,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2012,6]]}},"alternative-id":["S0959437X12000251"],"URL":"https:\/\/doi.org\/10.1016\/j.gde.2012.03.001","relation":{},"ISSN":["0959-437X"],"issn-type":[{"value":"0959-437X","type":"print"}],"subject":[],"published":{"date-parts":[[2012,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Accessing na\u00efve human pluripotency","name":"articletitle","label":"Article Title"},{"value":"Current Opinion in Genetics & Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.gde.2012.03.001","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2012 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}