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Adv."],"published-print":{"date-parts":[[2026,10,9]]},"abstract":"<jats:p>\n                    The cis-regulatory potential of human endogenous retroviruses (HERVs) that have accumulated in our genome affects diverse host processes, including embryonic development and malignancy, where HERV epigenetic control is reduced. Non\u2013small cell lung cancer optimal growth requires cancer cell\u2013intrinsic expression of the calcium-binding protein calbindin under the control of a\n                    <jats:italic toggle=\"yes\">HERVH<\/jats:italic>\n                    integrant on chromosome 8q21.3. Chimeric transcription of\n                    <jats:italic toggle=\"yes\">HERVH<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">CALB1<\/jats:italic>\n                    , encoding calbindin, is also observed in human embryonic stem cells (ESCs), but its significance remained uncertain. Here, we show that\n                    <jats:italic toggle=\"yes\">HERVH<\/jats:italic>\n                    integration on 8q21.3 during\n                    <jats:italic toggle=\"yes\">Homininae<\/jats:italic>\n                    evolution coincides with acquisition of expression of\n                    <jats:italic toggle=\"yes\">CALB1<\/jats:italic>\n                    in preimplantation embryos. We further show that\n                    <jats:italic toggle=\"yes\">CALB1<\/jats:italic>\n                    expression is critical for human ESC growth and the prevention of cellular senescence and for the formation of ESC-derived preimplantation blastoids and postgastrulation amnioids. Thus, the co-option of\n                    <jats:italic toggle=\"yes\">HERVH 8q21.3<\/jats:italic>\n                    cis-regulatory activity in lung cancer may echo its essential requirement for human embryo development.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aee4523","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:58:33Z","timestamp":1791395913000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Endogenous retrovirus control of calbindin is essential for human early embryogenesis"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4225-5568","authenticated-orcid":true,"given":"Judith","family":"Pape","sequence":"first","affiliation":[{"name":"Retroviral Immunology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afshan","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Human Embryo and Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5906-4127","authenticated-orcid":true,"given":"Eduardo","family":"Serna-Morales","sequence":"additional","affiliation":[{"name":"Cell and Tissue Mechanobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."},{"name":"Department of Physics, King\u2019s College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9379-3929","authenticated-orcid":true,"given":"Borzo","family":"Gharibi","sequence":"additional","affiliation":[{"name":"Quantitative Stem Cell Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0413-0975","authenticated-orcid":true,"given":"Tobias","family":"Plowman","sequence":"additional","affiliation":[{"name":"Retroviral Immunology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6831-5568","authenticated-orcid":true,"given":"Elias","family":"Copin","sequence":"additional","affiliation":[{"name":"Quantitative Stem Cell Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael","family":"Thompson","sequence":"additional","affiliation":[{"name":"Retroviral Immunology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Doglio","sequence":"additional","affiliation":[{"name":"Retroviral Immunology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1305-8821","authenticated-orcid":true,"given":"Ruta","family":"Meleckyte-Martinez","sequence":"additional","affiliation":[{"name":"Stem Cells and Organoids Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7044-8789","authenticated-orcid":true,"given":"Lyn","family":"Healy","sequence":"additional","affiliation":[{"name":"Stem Cells and Organoids Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0386-3788","authenticated-orcid":true,"given":"Sara","family":"Tamagno","sequence":"additional","affiliation":[{"name":"Stem Cells and Organoids Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0644-3294","authenticated-orcid":true,"given":"Alberto","family":"Elosegui-Artola","sequence":"additional","affiliation":[{"name":"Cell and Tissue Mechanobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK."},{"name":"Department of Physics, King\u2019s College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2906-7888","authenticated-orcid":true,"given":"Silvia D. 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