{"id":["DOI:10.1016/j.cell.2025.10.027"],"title":["Modeling human embryo implantation in vitro"],"publication_date":["2026-01-08"],"authors":{"ORCID:0000-0001-7342-4849":{"id":["ORCID:0000-0001-7342-4849"],"family_name":["Molè"],"personal_name":["Matteo A."],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]},"ROR:00f54p054":{"organization_name":["Stanford University"]},"ROR:02vbab064":{"organization_name":["Stanford Institute for Stem Cell Biology and Regenerative Medicine"]}},"HDBItheme":["Early"]},"ORCID:0000-0003-4861-8638":{"id":["ORCID:0000-0003-4861-8638"],"family_name":["Elderkin"],"personal_name":["Sarah"],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]}}},"ORCID:0000-0002-9229-5293":{"id":["ORCID:0000-0002-9229-5293"],"family_name":["Zorzan"],"personal_name":["Irene"],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham 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Research"]}}},"AUTHTEMP:00048":{"id":["AUTHTEMP:00048"],"family_name":["Fernando"],"personal_name":["Ridma C."],"affiliations":{"ROR:01bmjkv45":{"organization_name":["Friedrich Miescher Institute for Biomedical Research"]}}},"ORCID:0009-0005-5450-8496":{"id":["ORCID:0009-0005-5450-8496"],"family_name":["McCarthy"],"personal_name":["Afshan"],"affiliations":{"ROR:013meh722":{"organization_name":["University of Cambridge"]}},"HDBItheme":["Early"]},"ORCID:0000-0002-3515-9252":{"id":["ORCID:0000-0002-3515-9252"],"family_name":["Aghajanova"],"personal_name":["Lusine"],"affiliations":{"ROR:00f54p054":{"organization_name":["Stanford University"]}}},"ORCID:0009-0008-4803-4388":{"id":["ORCID:0009-0008-4803-4388"],"family_name":["Nel-Themaat"],"personal_name":["Liesl"],"affiliations":{"ROR:00f54p054":{"organization_name":["Stanford University"]}}},"ORCID:0000-0003-2159-2714":{"id":["ORCID:0000-0003-2159-2714"],"family_name":["Lathi"],"personal_name":["Ruth B."],"affiliations":{"ROR:00f54p054":{"organization_name":["Stanford University"]}}},"ORCID:0000-0001-9087-1616":{"id":["ORCID:0000-0001-9087-1616"],"family_name":["Cook"],"personal_name":["Simon J."],"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"]},"AUTHTEMP:00049":{"id":["AUTHTEMP:00049"],"family_name":["Dunn"],"personal_name":["Alexander R."],"affiliations":{"ROR:00f54p054":{"organization_name":["Stanford University"]}}},"ORCID:0000-0002-7620-8081":{"id":["ORCID:0000-0002-7620-8081"],"family_name":["Domínguez"],"personal_name":["Francisco"],"affiliations":{"ROR:00f54p054":{"organization_name":["Stanford University"]},"ROR:05n7v5997":{"organization_name":["Instituto de Investigación Sanitaria La Fe"]}}},"ORCID:0000-0002-9601-5949":{"id":["ORCID:0000-0002-9601-5949"],"family_name":["Rugg-Gunn"],"personal_name":["Peter J."],"affiliations":{"1":{}},"HDBItheme":["Early"]}},"abstract":["Implantation of a human embryo into the endometrium is a crucial event in gestation, as it marks the initiation of a pregnancy and is prone to high failure rates. We have limited understanding of these stages because of the inaccessibility of implanting embryos and the lack of suitable model systems. Here, we establish an in vitro model that recapitulates the luminal, glandular, and stromal compartments of the superficial layer of receptive human endometrium. Human embryos and blastoids implant into the endometrial model, achieving post-implantation hallmarks including advanced trophoblast structures that underlie early events in placental development. Single-cell RNA sequencing of the embryo-endometrial interface at day 14 uncovers predicted molecular interactions between conceptus and endometrium. Disrupting signaling interactions between extravillous trophoblast and endometrial stromal cells caused defects in trophoblast outgrowth, demonstrating the importance of crosstalk processes to sustain embryogenesis. This platform opens the opportunity to investigate early stages of human embryo implantation."],"HDBItheme":["Early"],"protocols":{"DOI:10.17504/protocols.io.rm7vzx67xgx1/v1":{"id":["DOI:10.17504/protocols.io.rm7vzx67xgx1/v1"],"title":["Endrometrial Scaffold Culture System"],"description":["This is a collection of protocols for culturing human embryos and human stem cell-derived blastoids in an endometrial culture system.\nThis culture system is comprised of multiple parts which have been broken out into separate protocols according to logical sections of work.\nThis list of protocols below is the place to start and to get an overview of the process. Some aspects of this process need to be performed in parallel so that all of the components are ready to be included in the culture system at the appropriate time.\nThe steps to perform to prepare the endometrial culture system are:\n- Isolation of Cells from Human Endometrial Biopsies - Culture of Human Endometrial Stromal Cells - Culture of Human Endometrial Epithelial Cells - Assembly of Endometrial Scaffold Systems\nIf you are culturing human embryos then follow:\n- Human Embryo Thawing\nIf you are culturing human blastoids then follow:\n- Culture of Human Pluripotent Stem Cells in Naïve Conditions Generation of Blastoids\nFinally, the protocol for culturing embryos or blastoids in the endometrial system is:\n- Human Embryo or Blastoid Culture in Endometrial Scaffolds\nEach protocol links to any pre-requisite protocols within it so as to be clear what steps need to have been performed before beginning any step."],"authors":{"ORCID:0000-0001-7342-4849":{"id":["ORCID:0000-0001-7342-4849"],"family_name":["Molè"],"personal_name":["Matteo A."],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]},"ROR:00f54p054":{"organization_name":["Stanford University"]},"ROR:02vbab064":{"organization_name":["Stanford Institute for Stem Cell Biology and Regenerative Medicine"]}},"HDBItheme":["Early"]},"ORCID:0000-0003-4861-8638":{"id":["ORCID:0000-0003-4861-8638"],"family_name":["Elderkin"],"personal_name":["Sarah"],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]}}},"ORCID:0000-0002-9229-5293":{"id":["ORCID:0000-0002-9229-5293"],"family_name":["Zorzan"],"personal_name":["Irene"],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]}}},"ORCID:0000-0002-2712-2388":{"id":["ORCID:0000-0002-2712-2388"],"family_name":["Horsley"],"personal_name":["Nicole"],"affiliations":{"ROR:00f54p054":{"organization_name":["Stanford University"]},"ROR:02vbab064":{"organization_name":["Stanford Institute for Stem Cell Biology and Regenerative Medicine"]}}},"ORCID:0000-0002-7620-8081":{"id":["ORCID:0000-0002-7620-8081"],"family_name":["Domínguez"],"personal_name":["Francisco"],"affiliations":{"ROR:00f54p054":{"organization_name":["Stanford University"]},"ROR:05n7v5997":{"organization_name":["Instituto de Investigación Sanitaria La Fe"]}}},"ORCID:0000-0002-9601-5949":{"id":["ORCID:0000-0002-9601-5949"],"family_name":["Rugg-Gunn"],"personal_name":["Peter J."],"affiliations":{"1":{}},"HDBItheme":["Early"]}}}},"datasets":{"ArrayExpress:E-MTAB-13629":{"id":["ArrayExpress:E-MTAB-13629"],"title":["In vitro modelling of the human embryo implantation niche"],"description":["Single-cell RNA-sequencing (10X) data from a three-dimensional cell-engineered system for human implantation that closely recapitulates the cytoarchitecture and physiology of the receptive human endometrium"],"authors":{"ORCID:0000-0001-5823-4705":{"id":["ORCID:0000-0001-5823-4705"],"family_name":["Penfold"],"personal_name":["Christopher"],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]},"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:05nz0zp31":{"organization_name":["Wellcome/MRC Cambridge Stem Cell Institute"]}}},"ORCID:0000-0002-9601-5949":{"id":["ORCID:0000-0002-9601-5949"],"family_name":["Rugg-Gunn"],"personal_name":["Peter J."],"affiliations":{"1":{}},"HDBItheme":["Early"]},"ORCID:0000-0001-7342-4849":{"id":["ORCID:0000-0001-7342-4849"],"family_name":["Molè"],"personal_name":["Matteo A."],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]},"ROR:00f54p054":{"organization_name":["Stanford University"]},"ROR:02vbab064":{"organization_name":["Stanford Institute for Stem Cell Biology and Regenerative Medicine"]}},"HDBItheme":["Early"]}},"tags":["sequencing"]},"DOI:10.5281/zenodo.17930156":{"id":["DOI:10.5281/zenodo.17930156"],"title":["Processed data for CREST analysis"],"description":["Processed datasets for easy re-plotting of figures and further analysis of the CREST paper of Molè, Elderkin, Zorzan, Penfold, Horsley et al."],"authors":{"ORCID:0000-0001-5823-4705":{"id":["ORCID:0000-0001-5823-4705"],"family_name":["Penfold"],"personal_name":["Christopher"],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]},"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:05nz0zp31":{"organization_name":["Wellcome/MRC Cambridge Stem Cell Institute"]}}}},"tags":["sequencing"]}},"code":{"DOI:10.5281/zenodo.17955321":{"id":["DOI:10.5281/zenodo.17955321"],"title":["Rugg-Gunn-Lab/CREST: Publication release v1.0"],"description":["Code for analysis of data from cell-engineered receptive endometrial scaffold technology (CREST) by Molè et al."],"authors":{"ORCID:0000-0001-5823-4705":{"id":["ORCID:0000-0001-5823-4705"],"family_name":["Penfold"],"personal_name":["Christopher"],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]},"ROR:02hmmse52":{"organization_name":["The Loke Centre for Trophoblast Research"]},"ROR:05nz0zp31":{"organization_name":["Wellcome/MRC Cambridge Stem Cell Institute"]}}}}}}}