{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T05:01:44Z","timestamp":1780549304091,"version":"3.54.1"},"reference-count":128,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T00:00:00Z","timestamp":1758326400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HD108722"],"award-info":[{"award-number":["R01 HD108722"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35 GM131759"],"award-info":[{"award-number":["R35 GM131759"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["T32 HD087166"],"award-info":[{"award-number":["T32 HD087166"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Developmental Biology"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.ydbio.2025.09.008","type":"journal-article","created":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T06:31:46Z","timestamp":1758349906000},"page":"255-263","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Primitive means first, not worst: Critical roles for primitive endoderm in embryos and embryo models"],"prefix":"10.1016","volume":"528","author":[{"given":"Marcelio A.","family":"Shammami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa","family":"Virola-Iarussi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"McCrary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3755-8262","authenticated-orcid":false,"given":"Amy","family":"Ralston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ydbio.2025.09.008_bib1","doi-asserted-by":"crossref","DOI":"10.1016\/j.gde.2023.102069","article-title":"Shifting early embryology paradigms: applications of stem cell-based embryo models in bioengineering","volume":"81","author":"Abel","year":"2023","journal-title":"Curr. Opin. Genet. Dev."},{"key":"10.1016\/j.ydbio.2025.09.008_bib2","doi-asserted-by":"crossref","first-page":"3550","DOI":"10.1038\/s41467-022-30858-8","article-title":"NANOG initiates epiblast fate through the coordination of pluripotency genes expression","volume":"13","author":"All\u00e8gre","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ydbio.2025.09.008_bib3","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41586-022-05246-3","article-title":"Embryo model completes gastrulation to neurulation and organogenesis","volume":"610","author":"Amadei","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.ydbio.2025.09.008_bib4","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.devcel.2020.12.004","article-title":"Inducible stem-cell-derived embryos capture mouse morphogenetic events in vitro","volume":"56","author":"Amadei","year":"2021","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib5","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1038\/ncb3617","article-title":"Insulin fine-tunes self-renewal pathways governing naive pluripotency and extra-embryonic endoderm","volume":"19","author":"Anderson","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib6","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.ydbio.2011.10.015","article-title":"BMP4 signaling directs primitive endoderm-derived XEN cells to an extraembryonic visceral endoderm identity","volume":"361","author":"Artus","year":"2012","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib7","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1242\/dev.050864","article-title":"A role for PDGF signaling in expansion of the extra-embryonic endoderm lineage of the mouse blastocyst","volume":"137","author":"Artus","year":"2010","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2025.09.008_bib8","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.devcel.2024.03.029","article-title":"Unlocking trophectoderm mysteries: in vivo and in vitro perspectives on human and mouse trophoblast fate induction","volume":"59","author":"Azagury","year":"2024","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib9","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/35001072","article-title":"The organizer factors chordin and noggin are required for mouse forebrain development","volume":"403","author":"Bachiller","year":"2000","journal-title":"Nature"},{"key":"10.1016\/j.ydbio.2025.09.008_bib10","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.stem.2017.12.011","article-title":"Capturing totipotent stem cells","volume":"22","author":"Baker","year":"2018","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib11","series-title":"Current Topics in Developmental Biology, Cell Fate in Mammalian Development","first-page":"81","article-title":"Chapter five - primitive endoderm differentiation: from specification to epithelialization","author":"Bassalert","year":"2018"},{"key":"10.1016\/j.ydbio.2025.09.008_bib12","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/s41556-024-01431-w","article-title":"Extraembryonic gut endoderm cells undergo programmed cell death during development","volume":"26","author":"Batki","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib13","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1242\/dev.105.4.733","article-title":"An assessment of the developmental potential of embryonic stem cells in the midgestation mouse embryo","volume":"105","author":"Beddington","year":"1989","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2025.09.008_bib14","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0059528","article-title":"p38 MAPK regulates cavitation and tight junction function in the mouse blastocyst","volume":"8","author":"Bell","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.ydbio.2025.09.008_bib15","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0925-4773(97)00125-1","article-title":"Cerberus-like is a secreted factor with neuralizing activity expressed in the anterior primitive endoderm of the mouse gastrula","volume":"68","author":"Belo","year":"1997","journal-title":"Mech. Dev."},{"key":"10.1016\/j.ydbio.2025.09.008_bib16","doi-asserted-by":"crossref","first-page":"3637","DOI":"10.1242\/dev.109678","article-title":"Gata6, nanog and erk signaling control cell fate in the inner cell mass through a tristable regulatory network","volume":"141","author":"Bessonnard","year":"2014","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2025.09.008_bib17","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1006\/dbio.1997.8812","article-title":"Murine cerberus homologue mCer-1: a candidate anterior patterning molecule","volume":"194","author":"Biben","year":"1998","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib18","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.1242\/dev.094458","article-title":"Porcn-dependent wnt signaling is not required prior to mouse gastrulation","volume":"140","author":"Biechele","year":"2013","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2025.09.008_bib19","doi-asserted-by":"crossref","first-page":"3613","DOI":"10.1242\/dev.131235","article-title":"Defining the three cell lineages of the human blastocyst by single-cell RNA-Seq","volume":"142","author":"Blakeley","year":"2015","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2025.09.008_bib20","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1038\/s42003-021-02290-z","article-title":"p38-MAPK-mediated translation regulation during early blastocyst development is required for primitive endoderm differentiation in mice","volume":"4","author":"Bora","year":"2021","journal-title":"Commun. Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib21","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.devcel.2015.10.011","article-title":"Lineage-specific profiling delineates the emergence and progression of naive pluripotency in Mammalian embryogenesis","volume":"35","author":"Boroviak","year":"2015","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib22","doi-asserted-by":"crossref","DOI":"10.1002\/wdev.259","article-title":"Properties of embryoid bodies","volume":"6","author":"Brickman","year":"2017","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib23","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1000379","article-title":"Functional heterogeneity of embryonic stem cells revealed through translational amplification of an early endodermal transcript","volume":"8","author":"Canham","year":"2010","journal-title":"PLoS Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib24","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0950-3552(05)80077-X","article-title":"Frequency of implantation and early pregnancy loss in natural cycles","volume":"5","author":"Chard","year":"1991","journal-title":"Baillieres Clin Obstet Gynaecol"},{"key":"10.1016\/j.ydbio.2025.09.008_bib25","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.devcel.2006.02.020","article-title":"Early lineage segregation between epiblast and primitive endoderm in mouse blastocysts through the Grb2-MAPK pathway","volume":"10","author":"Chazaud","year":"2006","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib26","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.1242\/dev.078519","article-title":"Conversion from mouse embryonic to extra-embryonic endoderm stem cells reveals distinct differentiation capacities of pluripotent stem cell states","volume":"139","author":"Cho","year":"2012","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2025.09.008_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2024.113701","article-title":"Molecular profiling of human blastocysts reveals primitive endoderm defects among embryos of decreased implantation potential","volume":"43","author":"Chousal","year":"2024","journal-title":"Cell Rep."},{"key":"10.1016\/j.ydbio.2025.09.008_bib28","doi-asserted-by":"crossref","DOI":"10.1002\/bies.201700239","article-title":"Identifying human na\u00efve pluripotent stem cells \u2212 evaluating state-specific reporter lines and cell-surface markers","volume":"40","author":"Collier","year":"2018","journal-title":"Bioessays"},{"key":"10.1016\/j.ydbio.2025.09.008_bib29","doi-asserted-by":"crossref","first-page":"6755","DOI":"10.1038\/s41467-022-34294-6","article-title":"The first mitotic division of human embryos is highly error prone","volume":"13","author":"Currie","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ydbio.2025.09.008_bib30","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1016\/j.stem.2024.05.003","article-title":"Naive pluripotent stem cell-based models capture FGF-dependent human hypoblast lineage specification","volume":"31","author":"Dattani","year":"2024","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib31","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/380037a0","article-title":"A common plan for dorsoventral patterning in Bilateria","volume":"380","author":"De Robertis","year":"1996","journal-title":"Nature"},{"key":"10.1016\/j.ydbio.2025.09.008_bib32","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1101\/gad.294004","article-title":"BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo","volume":"18","author":"de Sousa Lopes","year":"2004","journal-title":"Genes Dev."},{"key":"10.1016\/j.ydbio.2025.09.008_bib33","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nature17948","article-title":"Self-organization of the in vitro attached human embryo","volume":"533","author":"Deglincerti","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.ydbio.2025.09.008_bib34","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1111\/joa.12515","article-title":"From cradle to grave via the dissection room: the role of foetal and infant bodies in anatomical education from the late 1700s to early 1900s","volume":"229","author":"Dittmar","year":"2016","journal-title":"J. Anat."},{"key":"10.1016\/j.ydbio.2025.09.008_bib35","first-page":"27","article-title":"The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium","volume":"87","author":"Doetschman","year":"1985","journal-title":"J. Embryol. Exp. Morphol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib36","doi-asserted-by":"crossref","DOI":"10.1098\/rstb.2021.0251","article-title":"The mouse allantois: new insights at the embryonic\u2013extraembryonic interface","volume":"377","author":"Downs","year":"2022","journal-title":"Phil. Trans. Biol. Sci."},{"key":"10.1016\/j.ydbio.2025.09.008_bib37","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.ydbio.2025.09.008_bib38","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1002\/wdev.97","article-title":"Birth defects associated with perturbations in preimplantation, gastrulation, and axis extension: from conjoined twinning to caudal dysgenesis","volume":"2","author":"Ferrer-Vaquer","year":"2013","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib39","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.devcel.2011.10.019","article-title":"Primitive endoderm differentiates via a three-step mechanism involving nanog and RTK signaling","volume":"21","author":"Frankenberg","year":"2011","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib40","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1101\/gad.968802","article-title":"Differentiation of embryonic stem cells is induced by GATA factors","volume":"16","author":"Fujikura","year":"2002","journal-title":"Genes Dev."},{"key":"10.1016\/j.ydbio.2025.09.008_bib41","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/s41586-020-2759-x","article-title":"Initiation of a conserved trophectoderm program in human, cow and mouse embryos","volume":"587","author":"Gerri","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.ydbio.2025.09.008_bib42","doi-asserted-by":"crossref","DOI":"10.1126\/science.add7564","article-title":"Yolk sac cell atlas reveals multiorgan functions during human early development","volume":"381","author":"Goh","year":"2023","journal-title":"Science"},{"key":"10.1016\/j.ydbio.2025.09.008_bib43","doi-asserted-by":"crossref","DOI":"10.1126\/science.aal1810","article-title":"Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro","volume":"356","author":"Harrison","year":"2017","journal-title":"Science"},{"key":"10.1016\/j.ydbio.2025.09.008_bib44","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/aja.1000980306","article-title":"A description of 34 human ova within the first 17 days of development","volume":"98","author":"Hertig","year":"1956","journal-title":"Am. J. Anat."},{"key":"10.1016\/j.ydbio.2025.09.008_bib45","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41586-023-06914-8","article-title":"Modelling post-implantation human development to yolk sac blood emergence","volume":"626","author":"Hislop","year":"2024","journal-title":"Nature"},{"key":"10.1016\/j.ydbio.2025.09.008_bib46","first-page":"107","article-title":"In vitro development of inner cell masses isolated immunosurgically from mouse blastocysts. II. Inner cell masses from 3.5- to 4.0-day p.c. blastocysts","volume":"45","author":"Hogan","year":"1978","journal-title":"J. Embryol. Exp. Morphol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib47","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.devcel.2017.05.003","article-title":"Lineage establishment and progression within the inner cell mass of the mouse blastocyst requires FGFR1 and FGFR2","volume":"41","author":"Kang","year":"2017","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib48","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.devcel.2005.09.011","article-title":"Canonical wnt signaling and its antagonist regulate anterior-posterior axis polarization by guiding cell migration in mouse visceral endoderm","volume":"9","author":"Kimura-Yoshida","year":"2005","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib49","first-page":"312","article-title":"Human embryos commonly form abnormal nuclei during development: a mechanism of DNA damage, embryonic aneuploidy, and developmental arrest","volume":"31","author":"Kort","year":"2016","journal-title":"Hum. Reprod."},{"key":"10.1016\/j.ydbio.2025.09.008_bib50","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1242\/dev.071688","article-title":"The roles of FGF and MAP kinase signaling in the segregation of the epiblast and hypoblast cell lineages in bovine and human embryos","volume":"139","author":"Kuijk","year":"2012","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2025.09.008_bib51","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1242\/dev.01715","article-title":"Imprinted X-inactivation in extra-embryonic endoderm cell lines from mouse blastocysts","volume":"132","author":"Kunath","year":"2005","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2025.09.008_bib52","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.devcel.2008.07.017","article-title":"The endoderm of the mouse embryo arises by dynamic widespread intercalation of embryonic and extraembryonic lineages","volume":"15","author":"Kwon","year":"2008","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib53","doi-asserted-by":"crossref","DOI":"10.1038\/srep39457","article-title":"Efficient derivation of extraembryonic endoderm stem cell lines from mouse postimplantation embryos","volume":"6","author":"Lin","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ydbio.2025.09.008_bib54","doi-asserted-by":"crossref","first-page":"4010","DOI":"10.1016\/j.cell.2024.05.051","article-title":"The primitive endoderm supports lineage plasticity to enable regulative development","volume":"187","author":"Linneberg-Agerholm","year":"2024","journal-title":"Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib55","doi-asserted-by":"crossref","DOI":"10.1242\/dev.180620","article-title":"Na\u00efve human pluripotent stem cells respond to Wnt, nodal and LIF signalling to produce expandable na\u00efve extra-embryonic endoderm","volume":"146","author":"Linneberg-Agerholm","year":"2019","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2025.09.008_bib56","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1242\/dev.01729","article-title":"Requirement of the MAP kinase signaling pathways for mouse preimplantation development","volume":"132","author":"Maekawa","year":"2005","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2025.09.008_bib57","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. U. S. A"},{"key":"10.1016\/j.ydbio.2025.09.008_bib58","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1073\/pnas.72.4.1441","article-title":"Differentiation of clonal lines of teratocarcinoma cells: formation of embryoid bodies in vitro","volume":"72","author":"Martin","year":"1975","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ydbio.2025.09.008_bib59","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1038\/s41556-024-01492-x","article-title":"Criteria for the standardization of stem-cell-based embryo models","volume":"26","author":"Martinez Arias","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib60","doi-asserted-by":"crossref","DOI":"10.1098\/rstb.2021.0257","article-title":"Developmental and mechanical roles of Reichert's membrane in mouse embryos","volume":"377","author":"Matsuo","year":"2022","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"10.1016\/j.ydbio.2025.09.008_bib61","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.celrep.2014.09.026","article-title":"Sox17-Mediated XEN cell conversion identifies dynamic networks controlling cell-fate decisions in embryo-derived stem cells","volume":"9","author":"McDonald","year":"2014","journal-title":"Cell Rep."},{"key":"10.1016\/j.ydbio.2025.09.008_bib62","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1002\/dvdy.20135","article-title":"\u03b2-catenin signaling marks the prospective site of primitive streak formation in the mouse embryo","volume":"231","author":"Mohamed","year":"2004","journal-title":"Dev. Dyn."},{"key":"10.1016\/j.ydbio.2025.09.008_bib63","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.celrep.2017.07.009","article-title":"Single-cell landscape of transcriptional heterogeneity and cell fate decisions during mouse early gastrulation","volume":"20","author":"Mohammed","year":"2017","journal-title":"Cell Rep."},{"key":"10.1016\/j.ydbio.2025.09.008_bib64","doi-asserted-by":"crossref","first-page":"3679","DOI":"10.1038\/s41467-021-23758-w","article-title":"A single cell characterisation of human embryogenesis identifies pluripotency transitions and putative anterior hypoblast centre","volume":"12","author":"Mol\u00e8","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ydbio.2025.09.008_bib65","doi-asserted-by":"crossref","DOI":"10.1016\/j.ydbio.2018.07.010","article-title":"Distinct mechanisms for PDGF and FGF signaling in primitive endoderm development","author":"Molotkov","year":"2018","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib66","doi-asserted-by":"crossref","DOI":"10.1242\/dev.125021","article-title":"LIF supports primitive endoderm expansion during pre-implantation development","author":"Morgani","year":"2015","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2025.09.008_bib67","doi-asserted-by":"crossref","first-page":"8424","DOI":"10.1073\/pnas.90.18.8424","article-title":"Derivation of completely cell culture-derived mice from early-passage embryonic stem cells","volume":"90","author":"Nagy","year":"1993","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ydbio.2025.09.008_bib68","doi-asserted-by":"crossref","DOI":"10.1016\/j.ydbio.2012.12.008","article-title":"Analysis of human embryos from zygote to blastocyst reveals distinct gene expression patterns relative to the mouse","author":"Niakan","year":"2013","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib69","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1242\/dev.060426","article-title":"Human pre-implantation embryo development","volume":"139","author":"Niakan","year":"2012","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2025.09.008_bib70","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1101\/gad.1833510","article-title":"Sox17 promotes differentiation in mouse embryonic stem cells by directly regulating extraembryonic gene expression and indirectly antagonizing self-renewal","volume":"24","author":"Niakan","year":"2010","journal-title":"Genes Dev."},{"key":"10.1016\/j.ydbio.2025.09.008_bib71","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1038\/nprot.2013.049","article-title":"Derivation of extraembryonic endoderm stem (XEN) cells from mouse embryos and embryonic stem cells","volume":"8","author":"Niakan","year":"2013","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.ydbio.2025.09.008_bib72","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1242\/dev.038893","article-title":"Suppression of Erk signalling promotes ground state pluripotency in the mouse embryo","volume":"136","author":"Nichols","year":"2009","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2025.09.008_bib73","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1002\/dvdy.20405","article-title":"Experimental analysis of the transdifferentiation of visceral to parietal endoderm in the mouse","volume":"233","author":"Ninomiya","year":"2005","journal-title":"Dev. Dyn."},{"key":"10.1016\/j.ydbio.2025.09.008_bib74","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/s41586-019-1127-1","article-title":"The emergent landscape of the mouse gut endoderm at single-cell resolution","volume":"569","author":"Nowotschin","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.ydbio.2025.09.008_bib75","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1126\/science.aay3325","article-title":"Establishment of mouse stem cells that can recapitulate the developmental potential of primitive endoderm","volume":"375","author":"Ohinata","year":"2022","journal-title":"Science"},{"key":"10.1016\/j.ydbio.2025.09.008_bib76","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.cell.2009.03.014","article-title":"A signaling principle for the specification of the germ cell lineage in mice","volume":"137","author":"Ohinata","year":"2009","journal-title":"Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib77","doi-asserted-by":"crossref","DOI":"10.21769\/BioProtoc.4878","article-title":"Generation of mouse primitive endoderm stem cells","volume":"13","author":"Ohinata","year":"2023","journal-title":"Bio. Protoc."},{"key":"10.1016\/j.ydbio.2025.09.008_bib78","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ncb2881","article-title":"Cell-to-cell expression variability followed by signal reinforcement progressively segregates early mouse lineages","volume":"16","author":"Ohnishi","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib79","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/s41586-023-06604-5","article-title":"Complete human day 14 post-implantation embryo models from naive ES cells","volume":"622","author":"Oldak","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.ydbio.2025.09.008_bib80","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.ydbio.2011.10.013","article-title":"BMP signaling induces visceral endoderm differentiation of XEN cells and parietal endoderm","volume":"361","author":"Paca","year":"2012","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib81","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/S0301-472X(01)00669-5","article-title":"Yolk-sac hematopoiesis: the first blood cells of mouse and man","volume":"29","author":"Palis","year":"2001","journal-title":"Exp. Hematol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib82","article-title":"Mouse embryos, chimeras, and embryonal carcinoma stem cells-reflections on the winding road to gene manipulation","volume":"e2400061","author":"Papaioannou","year":"2024","journal-title":"Bioessays"},{"key":"10.1016\/j.ydbio.2025.09.008_bib83","doi-asserted-by":"crossref","DOI":"10.1016\/j.gde.2023.102115","article-title":"In vitro models of human hypoblast and mouse primitive endoderm","volume":"83","author":"Perera","year":"2023","journal-title":"Curr. Opin. Genet. Dev."},{"key":"10.1016\/j.ydbio.2025.09.008_bib84","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.cell.2016.03.023","article-title":"Single-cell RNA-seq reveals lineage and X chromosome dynamics in human preimplantation embryos","volume":"165","author":"Petropoulos","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib85","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ydbio.2023.07.002","article-title":"Transcriptional network governing extraembryonic endoderm cell fate choice","volume":"502","author":"Pham","year":"2023","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib86","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1242\/dev.021519","article-title":"Distinct sequential cell behaviours direct primitive endoderm formation in the mouse blastocyst","volume":"135","author":"Plusa","year":"2008","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2025.09.008_bib87","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nbt1263","article-title":"F0 generation mice fully derived from gene-targeted embryonic stem cells allowing immediate phenotypic analyses","volume":"25","author":"Poueymirou","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib88","doi-asserted-by":"crossref","first-page":"dev189845","DOI":"10.1242\/dev.189845","article-title":"From pluripotency to totipotency: an experimentalist's guide to cellular potency","volume":"147","author":"Riveiro","year":"2020","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2025.09.008_bib89","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ydbio.2017.08.026","article-title":"Visceral endoderm and the primitive streak interact to build the fetal-placental interface of the mouse gastrula","volume":"432","author":"Rodriguez","year":"2017","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib90","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 signalling","volume":"361","author":"Roode","year":"2012","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib91","doi-asserted-by":"crossref","first-page":"3760","DOI":"10.1038\/s41467-020-17575-w","article-title":"Origin and function of the yolk sac in primate embryogenesis","volume":"11","author":"Ross","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ydbio.2025.09.008_bib92","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/s41556-022-00923-x","article-title":"Identification of the central intermediate in the extra-embryonic to embryonic endoderm transition through single-cell transcriptomics","volume":"24","author":"Rothov\u00e1","year":"2022","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib93","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.devcel.2019.10.011","article-title":"Lumen expansion facilitates epiblast-primitive endoderm fate specification during mouse blastocyst formation","volume":"51","author":"Ryan","year":"2019","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib94","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.devcel.2014.04.011","article-title":"GATA6 levels modulate primitive endoderm cell fate choice and timing in the mouse blastocyst","volume":"29","author":"Schrode","year":"2014","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib95","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.stem.2008.06.018","article-title":"Establishment of endoderm progenitors by SOX transcription factor expression in human embryonic stem cells","volume":"3","author":"S\u00e9guin","year":"2008","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-09052-w","article-title":"Genetic dissection of nodal and Bmp signalling requirements during primordial germ cell development in mouse","volume":"10","author":"Senft","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ydbio.2025.09.008_bib97","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/ncb3347","article-title":"Self-organization of the human embryo in the absence of maternal tissues","volume":"18","author":"Shahbazi","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib98","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.stem.2024.09.002","article-title":"Early human development and stem cell-based human embryo models","volume":"31","author":"Shahbazi","year":"2024","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib99","author":"Simon"},{"key":"10.1016\/j.ydbio.2025.09.008_bib100","doi-asserted-by":"crossref","DOI":"10.1002\/bies.202400108","article-title":"Propagating pluripotency \u2013 the conundrum of self-renewal","volume":"46","author":"Smith","year":"2024","journal-title":"Bioessays"},{"key":"10.1016\/j.ydbio.2025.09.008_bib101","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/s41556-018-0147-7","article-title":"Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures","volume":"20","author":"Sozen","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib102","doi-asserted-by":"crossref","DOI":"10.1098\/rstb.2013.0546","article-title":"Heading forwards: anterior visceral endoderm migration in patterning the mouse embryo","volume":"369","author":"Stower","year":"2014","journal-title":"Phil. Trans. Biol. Sci."},{"key":"10.1016\/j.ydbio.2025.09.008_bib103","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.ydbio.2025.09.008_bib104","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 and adult fibroblast cultures by defined factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib105","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1038\/s41467-017-01625-x","article-title":"Both nodal signalling and stochasticity select for prospective distal visceral endoderm in mouse embryos","volume":"8","author":"Takaoka","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ydbio.2025.09.008_bib106","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/ncb2251","article-title":"Origin and role of distal visceral endoderm, a group of cells that determines anterior\u2013posterior polarity of the mouse embryo","volume":"13","author":"Takaoka","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib107","doi-asserted-by":"crossref","DOI":"10.1016\/j.crmeth.2023.100460","article-title":"Self-organized yolk sac-like organoids allow for scalable generation of multipotent hematopoietic progenitor cells from induced pluripotent stem cells","volume":"3","author":"Tamaoki","year":"2023","journal-title":"Cell Reports Methods"},{"key":"10.1016\/j.ydbio.2025.09.008_bib108","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1126\/science.282.5396.2072","article-title":"Promotion of trophoblast stem cell proliferation by FGF4","volume":"282","author":"Tanaka","year":"1998","journal-title":"Science"},{"key":"10.1016\/j.ydbio.2025.09.008_bib109","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.stem.2008.09.013","article-title":"Wnt signaling mediates self-organization and axis formation in embryoid bodies","volume":"3","author":"ten Berge","year":"2008","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib110","doi-asserted-by":"crossref","DOI":"10.1098\/rsob.160190","article-title":"p38 (Mapk14\/11) occupies a regulatory node governing entry into primitive endoderm differentiation during preimplantation mouse embryo development","volume":"6","author":"Thamodaran","year":"2016","journal-title":"Open Biol"},{"key":"10.1016\/j.ydbio.2025.09.008_bib111","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1016\/S0960-9822(96)00753-1","article-title":"Anterior primitive endoderm may be responsible for patterning the anterior neural plate in the mouse embryo","volume":"6","author":"Thomas","year":"1996","journal-title":"Curr. Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib112","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.ydbio.2025.09.008_bib113","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/s41586-021-04158-y","article-title":"Single-cell transcriptomic characterization of a gastrulating human embryo","volume":"600","author":"Tyser","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.ydbio.2025.09.008_bib114","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1101\/gad.257071.114","article-title":"Gata6 potently initiates reprograming of pluripotent and differentiated cells to extraembryonic endoderm stem cells","volume":"29","author":"Wamaitha","year":"2015","journal-title":"Genes Dev."},{"key":"10.1016\/j.ydbio.2025.09.008_bib115","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0015-0282(02)04694-0","article-title":"Conception, early pregnancy loss, and time to clinical pregnancy: a population-based prospective study","volume":"79","author":"Wang","year":"2003","journal-title":"Fertil. Steril."},{"key":"10.1016\/j.ydbio.2025.09.008_bib116","first-page":"1","article-title":"Distinct pathways drive anterior hypoblast specification in the implanting human embryo","author":"Weatherbee","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib117","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1004618","article-title":"HIPPO pathway members restrict SOX2 to the inner cell mass where it promotes ICM fates in the mouse blastocyst","volume":"10","author":"Wicklow","year":"2014","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ydbio.2025.09.008_bib118","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1056\/NEJM198807283190401","article-title":"Incidence of early loss of pregnancy","volume":"319","author":"Wilcox","year":"1988","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ydbio.2025.09.008_bib119","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/shm\/hku071","article-title":"From women's expectations to scientific specimens: the fate of miscarriage materials in nineteenth-century America","volume":"28","author":"Withycombe","year":"2015","journal-title":"Soc. Hist. Med."},{"key":"10.1016\/j.ydbio.2025.09.008_bib120","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1038\/ncb2267","article-title":"Inhibition of glycogen synthase kinase-3 alleviates Tcf3 repression of the pluripotency network and increases embryonic stem cell resistance to differentiation","volume":"13","author":"Wray","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib121","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nature02418","article-title":"Nodal antagonists regulate formation of the anteroposterior axis of the mouse embryo","volume":"428","author":"Yamamoto","year":"2004","journal-title":"Nature"},{"key":"10.1016\/j.ydbio.2025.09.008_bib122","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1242\/dev.043471","article-title":"FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst","volume":"137","author":"Yamanaka","year":"2010","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2025.09.008_bib123","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.ydbio.2025.09.008_bib124","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1006\/dbio.2001.0173","article-title":"Cooperation of endoderm-derived BMP2 and extraembryonic ectoderm-derived BMP4 in primordial germ cell generation in the mouse","volume":"232","author":"Ying","year":"2001","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2025.09.008_bib125","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1126\/science.1151526","article-title":"Induced pluripotent stem cell lines derived from human somatic cells","volume":"318","author":"Yu","year":"2007","journal-title":"Science"},{"key":"10.1016\/j.ydbio.2025.09.008_bib126","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/s41586-019-1500-0","article-title":"Reconstituting the transcriptome and DNA methylome landscapes of human implantation","volume":"572","author":"Zhou","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.ydbio.2025.09.008_bib127","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.devcel.2022.12.004","article-title":"Decoding anterior-posterior axis emergence among mouse, monkey, and human embryos","volume":"58","author":"Zhu","year":"2023","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ydbio.2025.09.008_bib128","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a033274","article-title":"TGF-\u03b2 family signaling in early vertebrate development","volume":"10","author":"Zinski","year":"2018","journal-title":"Cold Spring Harbor Perspect. Biol."}],"container-title":["Developmental Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0012160625002660?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0012160625002660?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:10:12Z","timestamp":1780546212000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0012160625002660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":128,"alternative-id":["S0012160625002660"],"URL":"https:\/\/doi.org\/10.1016\/j.ydbio.2025.09.008","relation":{},"ISSN":["0012-1606"],"issn-type":[{"value":"0012-1606","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Primitive means first, not worst: Critical roles for primitive endoderm in embryos and embryo models","name":"articletitle","label":"Article Title"},{"value":"Developmental Biology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ydbio.2025.09.008","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}