{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:39:00Z","timestamp":1760708340958,"version":"3.37.3"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2011,11,16]],"date-time":"2011-11-16T00:00:00Z","timestamp":1321401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Genome Technology Access Center of Washington University"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01-AG024250","R21-DC010489"],"award-info":[{"award-number":["R01-AG024250","R21-DC010489"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Model Animal Research Center of Nanjing University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Induced pluripotent stem cells (iPSCs) can be reprogrammed from adult somatic cells by transduction with Oct4, Sox2, Klf4, and c-Myc, but the molecular cascades initiated by these factors remain poorly understood. Impeding their elucidation is the stochastic nature of the iPS induction process, which results in heterogeneous cell populations. Here we have synchronized the reprogramming process by a two-phase induction: an initial stable intermediate phase following transduction with Oct4, Klf4, and c-Myc, and a final iPS phase following overexpression of Sox2. This approach has enabled us to examine temporal gene expression profiles, permitting the identification of Sox2 downstream genes critical for induction. Furthermore, we have validated the feasibility of our new approach by using it to confirm that downregulation of transforming growth factor \u03b2 signaling by Sox2 proves essential to the reprogramming process. Thus, we present a novel means for dissecting the details underlying the induction of iPSCs, an approach with significant utility in this arena and the potential for wide-ranging implications in the study of other reprogramming mechanisms.<\/jats:p>","DOI":"10.1002\/stem.752","type":"journal-article","created":{"date-parts":[[2011,9,28]],"date-time":"2011-09-28T20:51:36Z","timestamp":1317243096000},"page":"1963-1974","source":"Crossref","is-referenced-by-count":14,"title":["Two-Phase Analysis of Molecular Pathways Underlying Induced Pluripotent Stem Cell Induction"],"prefix":"10.1093","volume":"29","author":[{"given":"Zhaoyu","family":"Lin","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center of Nanjing University, Nanjing, Jiangsu, People's Republic of China"},{"name":"Fay Simon Center for Hearing Research at the Department of Otolaryngology, Washington University School of Medicine, St. Louis, Missouri, 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Gao","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center of Nanjing University, Nanjing, Jiangsu, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianxin","family":"Bao","sequence":"additional","affiliation":[{"name":"Fay Simon Center for Hearing Research at the Department of Otolaryngology, Washington University School of Medicine, St. Louis, Missouri, USA"},{"name":"Division of Biology & Biomedical Science and Neuroscience Program, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,11,16]]},"reference":[{"key":"2022011216084870900_bib1","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1038\/385810a0","article-title":"Viable offspring derived 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