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Results reveal a key period between weeks 4 and 6 with elevated intra-organoid oxygen tension, altered energy homeostasis, and rapid neurogenesis within the organoids. The timed oxygen tension elevation can be suppressed by hypoxia treatment or silencing of neuroglobin gene. This study provides insights into the role of oxygen in early neurogenesis from functional, genotypic, phenotypic, and proteomic aspects. These findings highlight the significance of the timed tissue oxygen tension elevation in neurogenesis and provide insights into the role of neuroglobin in neural development, with potential implications for understanding neurodegenerative diseases and therapeutic strategies.<\/jats:p>","DOI":"10.1126\/sciadv.ado1164","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T17:58:57Z","timestamp":1741802337000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":7,"title":["Shaping early neural development by timed elevated tissue oxygen tension: Insights from multiomic analysis on human cerebral organoids"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5695-5047","authenticated-orcid":true,"given":"Yuan-Hsuan","family":"Liu","sequence":"first","affiliation":[{"name":"Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7539-5893","authenticated-orcid":true,"given":"Meng-Ting","family":"Chung","sequence":"additional","affiliation":[{"name":"Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsi-Chieh","family":"Lin","sequence":"additional","affiliation":[{"name":"Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9565-399X","authenticated-orcid":true,"given":"Tse-Ang","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3743-5094","authenticated-orcid":true,"given":"Ya-Jen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan."},{"name":"Neuroscience Program of Academia Sinica, Academia Sinica, Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8089-251X","authenticated-orcid":true,"given":"Chien-Chang","family":"Huang","sequence":"additional","affiliation":[{"name":"SYNCELL Inc., Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7027-3069","authenticated-orcid":true,"given":"Hsiao-Mei","family":"Wu","sequence":"additional","affiliation":[{"name":"Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan."},{"name":"Department of Biomechatronics Engineering, National Taiwan University, Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6170-2992","authenticated-orcid":true,"given":"Yi-Chung","family":"Tung","sequence":"additional","affiliation":[{"name":"Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","first-page":"38","article-title":"Regulation of cerebral circulation","volume":"4","author":"Sokoloff L.","year":"1960","unstructured":"L. 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