{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:03:47Z","timestamp":1787321027422,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"am","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EB027391\u201001"],"award-info":[{"award-number":["EB027391\u201001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CBET1919830"],"award-info":[{"award-number":["CBET1919830"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CBET1928855"],"award-info":[{"award-number":["CBET1928855"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Human induced pluripotent stem cells (iPSCs) are an invaluable endless cell source for generating various therapeutic cells and tissues. However, their differentiation into specific cell lineages, such as definitive endoderm (DE) and pancreatic progenitor (PP), often suffers from poor reproducibility, due partially to their pluripotency. In this work, we investigated the impact of iPSC confluency during cell self\u2010renewal and seeding density on cell metabolic activity, glycolysis to oxidative phosphorylation shift, and differentiation potential toward DE and PP lineages. Our findings demonstrated that cell seeding strategy influences cellular metabolic activity and the robustness of iPSC differentiation. iPSCs maintained at higher seeding density exhibited lower initial oxygen consumption rate (OCR) and metabolic activity. There is an optimal seeding density to ensure sufficient oxygen consumption during differentiation and to yield high expression of SOX17 in the DE lineage and high PDX1\/NKX6.1 dual\u2010positive cells in PPs. Interestingly, we found that cell confluency at the time of harvest has less impact on the efficacy of pancreatic lineage formation or metabolic activity. This study sheds light on the interplay between metabolic activity and iPSC lineage specification, offering new insights into the robustness of iPSC self\u2010renewal and differentiation for creating human tissues.<\/jats:p>","DOI":"10.1002\/biot.70022","type":"journal-article","created":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T02:20:14Z","timestamp":1745634014000},"source":"Crossref","is-referenced-by-count":5,"title":["Cell Seeding Strategy Influences Metabolism and Differentiation Potency of Human Induced Pluripotent Stem Cells Into Pancreatic Progenitors"],"prefix":"10.1002","volume":"20","author":[{"given":"Hui","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Thomas J. Watson College of Engineering and Applied Science Binghamton University State University of New York (SUNY) Binghamton New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiming","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Thomas J. Watson College of Engineering and Applied Science Binghamton University State University of New York (SUNY) Binghamton New York USA"},{"name":"Center of Biomanufacturing for Regenerative Medicine Binghamton University State University of New York (SUNY) Binghamton New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8033-8110","authenticated-orcid":false,"given":"Sha","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Thomas J. Watson College of Engineering and Applied Science Binghamton University State University of New York (SUNY) Binghamton New York USA"},{"name":"Center of Biomanufacturing for Regenerative Medicine Binghamton University State University of New York (SUNY) Binghamton New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13121052"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10020208"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2022.06.014"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12101442"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2019.11.010"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-92922-5"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23525-x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3033"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2021.07.021"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2015.02.017"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.104883"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2016.0115"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202302275"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0271-4"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201500479"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2021.102534"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11111741"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2011.0474"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0501283102"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.524363"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1163"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007-0445"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00087"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.10.005"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.436"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-015-0007-9"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2011.0048"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2019.119673"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.0c00088"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.04.005"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.06.011"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113459"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-021-00560-y"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-016-1097-0"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.05.024"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.23603"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00227"}],"container-title":["Biotechnology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biot.70022","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biot.70022","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T19:52:16Z","timestamp":1759953136000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/biot.70022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":37,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/biot.70022"],"URL":"https:\/\/doi.org\/10.1002\/biot.70022","archive":["Portico"],"relation":{},"ISSN":["1860-6768","1860-7314"],"issn-type":[{"value":"1860-6768","type":"print"},{"value":"1860-7314","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4]]},"article-number":"e70022"}}