{"id":["DOI:10.1016/j.stem.2024.12.007"],"title":["Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome"],"publication_date":["2021-10-14"],"authors":{"ORCID:0009-0003-1386-3438":{"id":["ORCID:0009-0003-1386-3438"],"family_name":["Lea"],"personal_name":["Georgia"],"affiliations":{"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0000-0001-7064-2680":{"id":["ORCID:0000-0001-7064-2680"],"family_name":["Doria-Borrell"],"personal_name":["Paula"],"affiliations":{"ROR:05xr2yq54":{"organization_name":["Centro de Investigacion Principe Felipe"]}}},"ORCID:0009-0009-4530-1687":{"id":["ORCID:0009-0009-4530-1687"],"family_name":["Ferrero-Micó"],"personal_name":["Ana"],"affiliations":{"ROR:05xr2yq54":{"organization_name":["Centro de Investigacion Principe Felipe"]}}},"AUTHTEMP:00034":{"id":["AUTHTEMP:00034"],"family_name":["Varma"],"personal_name":["Anakha"],"affiliations":{"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0000-0001-9614-1403":{"id":["ORCID:0000-0001-9614-1403"],"family_name":["Simon"],"personal_name":["Claire S."],"affiliations":{"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0009-0006-9721-0048":{"id":["ORCID:0009-0006-9721-0048"],"family_name":["Anderson"],"personal_name":["Holly"],"affiliations":{"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0000-0002-0975-1121":{"id":["ORCID:0000-0002-0975-1121"],"family_name":["Biggins"],"personal_name":["Laura"],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]}}},"ORCID:0000-0002-7439-7587":{"id":["ORCID:0000-0002-7439-7587"],"family_name":["De Clercq"],"personal_name":["Katrien"],"affiliations":{"ROR:05f950310":{"organization_name":["KU Leuven"]}}},"ORCID:0000-0002-5006-3507":{"id":["ORCID:0000-0002-5006-3507"],"family_name":["Andrews"],"personal_name":["Simon"],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]}}},"ORCID:0000-0003-1646-4734":{"id":["ORCID:0000-0003-1646-4734"],"family_name":["Niakan"],"personal_name":["Kathy K."],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]},"ROR:05nz0zp31":{"organization_name":["Wellcome/MRC Cambridge Stem Cell Institute"]},"ROR:04tnbqb63":{"organization_name":["The Francis Crick Institute"]}},"HDBItheme":["Early"]},"ORCID:0000-0002-9412-7971":{"id":["ORCID:0000-0002-9412-7971"],"family_name":["Gahurova"],"personal_name":["Lenka"],"affiliations":{"ROR:033n3pw66":{"organization_name":["University of South Bohemia in České Budějovice"]}}},"ORCID:0000-0001-5200-2698":{"id":["ORCID:0000-0001-5200-2698"],"family_name":["McGovern"],"personal_name":["Naomi"],"affiliations":{"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0000-0001-5594-1607":{"id":["ORCID:0000-0001-5594-1607"],"family_name":["Pérez-García"],"personal_name":["Vicente"],"affiliations":{"ROR:05xr2yq54":{"organization_name":["Centro de Investigacion Principe Felipe"]},"ROR:03v9e8t09":{"organization_name":["Centro de Biología Molecular Severo Ochoa"]}}},"ORCID:0000-0002-4063-5575":{"id":["ORCID:0000-0002-4063-5575"],"family_name":["Hanna"],"personal_name":["Courtney W."],"affiliations":{"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]}}}},"abstract":["The placental DNA methylation landscape is unique, with widespread partially methylated domains (PMDs). The placental “methylome” is conserved across mammals, a shared feature of many cancers, and extensively studied for links with pregnancy complications. Human trophoblast stem cells (hTSCs) offer exciting potential for functional studies to better understand this epigenetic feature; however, whether the hTSC epigenome recapitulates primary trophoblast remains unclear. We find that hTSCs exhibit an atypical methylome compared with trophectoderm and 1st trimester cytotrophoblast. Regardless of cell origin, oxygen levels, or culture conditions, hTSCs show localized DNA methylation within transcribed gene bodies and a complete loss of PMDs. Unlike early human trophoblasts, hTSCs display a notable absence of DNMT3L expression, which is necessary for PMD establishment in mouse trophoblasts. Remarkably, we demonstrate that ectopic expression of DNMT3L in hTSCs restores placental PMDs, supporting a conserved role for DNMT3L in de novo methylation in trophoblast development in human embryogenesis."],"HDBItheme":["Early"],"datasets":{"GEO:GSE266196":{"id":["GEO:GSE266196"],"title":["Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome."],"description":["Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome."],"authors":{"ORCID:0000-0002-3511-9090":{"id":["ORCID:0000-0002-3511-9090"],"family_name":["Inglesfield"],"personal_name":["Sarah"],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]}}},"ORCID:0009-0003-1386-3438":{"id":["ORCID:0009-0003-1386-3438"],"family_name":["Lea"],"personal_name":["Georgia"],"affiliations":{"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0000-0001-7064-2680":{"id":["ORCID:0000-0001-7064-2680"],"family_name":["Doria-Borrell"],"personal_name":["Paula"],"affiliations":{"ROR:05xr2yq54":{"organization_name":["Centro de Investigacion Principe Felipe"]}}},"ORCID:0009-0009-4530-1687":{"id":["ORCID:0009-0009-4530-1687"],"family_name":["Ferrero-Micó"],"personal_name":["Ana"],"affiliations":{"ROR:05xr2yq54":{"organization_name":["Centro de Investigacion Principe Felipe"]}}},"ORCID:0000-0001-9614-1403":{"id":["ORCID:0000-0001-9614-1403"],"family_name":["Simon"],"personal_name":["Claire S."],"affiliations":{"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0009-0006-9721-0048":{"id":["ORCID:0009-0006-9721-0048"],"family_name":["Anderson"],"personal_name":["Holly"],"affiliations":{"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0000-0001-5200-2698":{"id":["ORCID:0000-0001-5200-2698"],"family_name":["McGovern"],"personal_name":["Naomi"],"affiliations":{"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0000-0001-5594-1607":{"id":["ORCID:0000-0001-5594-1607"],"family_name":["Pérez-García"],"personal_name":["Vicente"],"affiliations":{"ROR:05xr2yq54":{"organization_name":["Centro de Investigacion Principe Felipe"]},"ROR:03v9e8t09":{"organization_name":["Centro de Biología Molecular Severo Ochoa"]}}},"ORCID:0000-0002-4063-5575":{"id":["ORCID:0000-0002-4063-5575"],"family_name":["Hanna"],"personal_name":["Courtney W."],"affiliations":{"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]}}}},"tags":["sequencing"]},"EGA:EGAS50000000661":{"id":["EGA:EGAS50000000661"],"title":["PBAT sequencing of primary first trimester cytotrophoblast and mural trophectoderm."],"description":["To assess whether the DNA methylation landscape of human trophoblast stem cells resembles an in vivo cell type, we used post-bisulfite adaptor-tag sequencing to measure genome-wide DNA methylation of preimplantation human trophectoderm and sorted first trimester cytotrophoblast."],"authors":{"ORCID:0009-0003-1386-3438":{"id":["ORCID:0009-0003-1386-3438"],"family_name":["Lea"],"personal_name":["Georgia"],"affiliations":{"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0000-0001-7064-2680":{"id":["ORCID:0000-0001-7064-2680"],"family_name":["Doria-Borrell"],"personal_name":["Paula"],"affiliations":{"ROR:05xr2yq54":{"organization_name":["Centro de Investigacion Principe Felipe"]}}},"ORCID:0009-0009-4530-1687":{"id":["ORCID:0009-0009-4530-1687"],"family_name":["Ferrero-Micó"],"personal_name":["Ana"],"affiliations":{"ROR:05xr2yq54":{"organization_name":["Centro de Investigacion Principe Felipe"]}}},"ORCID:0000-0001-9614-1403":{"id":["ORCID:0000-0001-9614-1403"],"family_name":["Simon"],"personal_name":["Claire S."],"affiliations":{"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0009-0006-9721-0048":{"id":["ORCID:0009-0006-9721-0048"],"family_name":["Anderson"],"personal_name":["Holly"],"affiliations":{"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0000-0001-5200-2698":{"id":["ORCID:0000-0001-5200-2698"],"family_name":["McGovern"],"personal_name":["Naomi"],"affiliations":{"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0000-0001-5594-1607":{"id":["ORCID:0000-0001-5594-1607"],"family_name":["Pérez-García"],"personal_name":["Vicente"],"affiliations":{"ROR:05xr2yq54":{"organization_name":["Centro de Investigacion Principe Felipe"]},"ROR:03v9e8t09":{"organization_name":["Centro de Biología Molecular Severo Ochoa"]}}},"ORCID:0000-0002-4063-5575":{"id":["ORCID:0000-0002-4063-5575"],"family_name":["Hanna"],"personal_name":["Courtney W."],"affiliations":{"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]}}}},"tags":["sequencing"]},"DOI:10.17632/cc6ftgctbd.1":{"id":["DOI:10.17632/cc6ftgctbd.1"],"title":["Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome"],"description":["This dataset contains the raw western blot data related to the article titled \"Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome\". Specifically, it includes data for the blots shown in Figures 4c, 6d, and Supplementary Figure S6i.\""],"authors":{"ORCID:0009-0003-1386-3438":{"id":["ORCID:0009-0003-1386-3438"],"family_name":["Lea"],"personal_name":["Georgia"],"affiliations":{"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0000-0001-7064-2680":{"id":["ORCID:0000-0001-7064-2680"],"family_name":["Doria-Borrell"],"personal_name":["Paula"],"affiliations":{"ROR:05xr2yq54":{"organization_name":["Centro de Investigacion Principe Felipe"]}}},"ORCID:0009-0009-4530-1687":{"id":["ORCID:0009-0009-4530-1687"],"family_name":["Ferrero-Micó"],"personal_name":["Ana"],"affiliations":{"ROR:05xr2yq54":{"organization_name":["Centro de Investigacion Principe Felipe"]}}},"ORCID:0000-0001-9614-1403":{"id":["ORCID:0000-0001-9614-1403"],"family_name":["Simon"],"personal_name":["Claire S."],"affiliations":{"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0009-0006-9721-0048":{"id":["ORCID:0009-0006-9721-0048"],"family_name":["Anderson"],"personal_name":["Holly"],"affiliations":{"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0000-0001-5200-2698":{"id":["ORCID:0000-0001-5200-2698"],"family_name":["McGovern"],"personal_name":["Naomi"],"affiliations":{"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]}}},"ORCID:0000-0001-5594-1607":{"id":["ORCID:0000-0001-5594-1607"],"family_name":["Pérez-García"],"personal_name":["Vicente"],"affiliations":{"ROR:05xr2yq54":{"organization_name":["Centro de Investigacion Principe Felipe"]},"ROR:03v9e8t09":{"organization_name":["Centro de Biología Molecular Severo Ochoa"]}}},"ORCID:0000-0002-4063-5575":{"id":["ORCID:0000-0002-4063-5575"],"family_name":["Hanna"],"personal_name":["Courtney W."],"affiliations":{"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:013meh722":{"organization_name":["University of Cambridge"]}}}},"tags":["imaging"]}}}