{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T15:26:27Z","timestamp":1780327587012,"version":"3.54.1"},"reference-count":70,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"7","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,2,17]]},"abstract":"<jats:p>\n            <jats:italic>SMCHD1<\/jats:italic>\n            mutations cause congenital arhinia (absent nose) and a muscular dystrophy called FSHD2. In FSHD2, loss of SMCHD1 repressive activity causes expression of double homeobox 4 (DUX4) in muscle tissue, where it is toxic. Studies of arhinia patients suggest a primary defect in nasal placode cells (human nose progenitors). Here, we show that upon SMCHD1 ablation, DUX4 becomes derepressed in H9 human embryonic stem cells (hESCs) as they differentiate toward a placode cell fate, triggering cell death. Arhinia and FSHD2 patient-derived induced pluripotent stem cells (iPSCs) express DUX4 when converted to placode cells and demonstrate variable degrees of cell death, suggesting an environmental disease modifier. HSV-1 may be one such modifier as herpesvirus infection amplifies DUX4 expression in SMCHD1 KO hESC and patient iPSC. These studies suggest that arhinia, like FSHD2, is due to compromised SMCHD1 repressive activity in a cell-specific context and provide evidence for an environmental modifier.\n          <\/jats:p>","DOI":"10.1126\/sciadv.abq7744","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T18:58:22Z","timestamp":1676660302000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":10,"title":["DUX4 double whammy: The transcription factor that causes a rare muscular dystrophy also kills the precursors of the human nose"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3615-6192","authenticated-orcid":true,"given":"Kaoru","family":"Inoue","sequence":"first","affiliation":[{"name":"Pediatric Neuroendocrinology Group, Clinical Research Branch, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4102-807X","authenticated-orcid":true,"given":"Hamed","family":"Bostan","sequence":"additional","affiliation":[{"name":"Integrative Bioinformatics, NIEHS, Research Triangle Park, NC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9504-1611","authenticated-orcid":true,"given":"MaKenna R.","family":"Browne","sequence":"additional","affiliation":[{"name":"Pediatric Neuroendocrinology Group, Clinical Research Branch, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen F.","family":"Bevis","sequence":"additional","affiliation":[{"name":"Pediatric Neuroendocrinology Group, Clinical Research Branch, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5444-6628","authenticated-orcid":true,"given":"Carl D.","family":"Bortner","sequence":"additional","affiliation":[{"name":"Signal Transduction Laboratory, NIEHS, Research Triangle Park, NC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa Carver College of Medicine and Senator Paul D.\u00a0Wellstone Muscular Dystrophy Specialized Research Center, Iowa City, IA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron A.","family":"Stence","sequence":"additional","affiliation":[{"name":"University of Iowa Hospitals and Clinics, Iowa City, IA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3166-8989","authenticated-orcid":true,"given":"Negin P.","family":"Martin","sequence":"additional","affiliation":[{"name":"Viral Vector Core, NIEHS, Research Triangle Park, NC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Heng","family":"Chen","sequence":"additional","affiliation":[{"name":"Viral Vector Core, NIEHS, Research Triangle Park, NC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam B.","family":"Burkholder","sequence":"additional","affiliation":[{"name":"Integrative Bioinformatics, NIEHS, Research Triangle Park, NC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6487-081X","authenticated-orcid":true,"given":"Jian-Liang","family":"Li","sequence":"additional","affiliation":[{"name":"Integrative Bioinformatics, NIEHS, Research Triangle Park, NC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0847-9170","authenticated-orcid":true,"given":"Natalie 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des placodes olfactives et des ebauches optiques sur la morphagenese du squelette cranien chez Pleurodeles waltii michah","volume":"1","author":"Corsin J.","year":"1971","unstructured":"J.\u00a0Corsin, Influence des placodes olfactives et des ebauches optiques sur la morphagenese du squelette cranien chez Pleurodeles waltii michah. 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M.\u00a0Novoa-Del-Toro, R.\u00a0Chevalier, N.\u00a0Broucqsault, V. V.\u00a0Rao, J. P.\u00a0Trani, K.\u00a0Nguyen, S.\u00a0Xue, B.\u00a0Reversade, J. D.\u00a0Robin, A.\u00a0Baudot, F.\u00a0Magdinier, AKT signaling modifies the balance between cell proliferation and migration in neural crest cells from patients affected with bosma arhinia and microphthalmia syndrome. Biomedicine 9, 751 (2021).","journal-title":"Biomedicine"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00893-0"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0501916102"},{"key":"e_1_3_2_50_2","doi-asserted-by":"crossref","unstructured":"S. Walter V.\u00a0Franke N.\u00a0Drayman E.\u00a0Wyler S.\u00a0Tay M.\u00a0Landthaler A.\u00a0Akalin A.\u00a0Ensser F.\u00a0Full Herpesviral induction of germline transcription factor DUX4 is critical for viral gene expression. bioRxiv 2021.03.24.436599 [ Preprint ]. 24 March 2021. https:\/\/doi.org\/10.1101\/2021.03.24.436599.","DOI":"10.1101\/2021.03.24.436599"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1701-2163(16)32868-7"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep11319"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2899"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1172482"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc3851"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth1010"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.10.6043"},{"key":"e_1_3_2_58_2","first-page":"Unit 4.21","article-title":"Production and titration of lentiviral vectors","volume":"4","author":"Barde I.","year":"2010","unstructured":"I.\u00a0Barde, P.\u00a0Salmon, D.\u00a0Trono, Production and titration of lentiviral vectors. 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(University of Washington Seattle 1993)."},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2021.07.021"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1923"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty648"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2004-5-10-r80"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.05.004"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.24956.1"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.abq7744","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T21:14:02Z","timestamp":1704834842000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.abq7744"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,17]]},"references-count":70,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,2,17]]}},"alternative-id":["10.1126\/sciadv.abq7744"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.abq7744","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,17]]},"assertion":[{"value":"2022-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eabq7744"}}