{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T23:17:13Z","timestamp":1767914233651,"version":"3.49.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T00:00:00Z","timestamp":1730678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"am","delay-in-days":365,"URL":"http:\/\/rsc.li\/journals-terms-of-use"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JPJSCCA20190006"],"award-info":[{"award-number":["JPJSCCA20190006"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004562","name":"Minist\u00e8re de l'Enseignement sup\u00e9rieur et de la Recherche","doi-asserted-by":"publisher","award":["Unassigned"],"award-info":[{"award-number":["Unassigned"]}],"id":[{"id":"10.13039\/501100004562","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JPJSCCA20190006"],"award-info":[{"award-number":["JPJSCCA20190006"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004562","name":"Minist\u00e8re de l'Enseignement sup\u00e9rieur et de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004562","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rsc.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pancreatic \u03b2-cells are composed of different subtypes that play a key role in the control of insulin secretion and thereby control glucose homeostasis. In vitro differentiation of human induced pluripotent stem cells (hiPSCs) into 3D spheroids leads to the generation of \u03b2-cell subtypes and thus to the development of islet-like structures. Using this cutting-edge cell model, the aim of the study was to decipher the signaling signature that underlines \u03b2-cell subtypes, with a focus on the search for the activity of motifs of important transcription regulators (TRs). The investigation was performed using data from previous single-cell sequencing analysis introduced into the integrated system for motif activity response analysis (ISMARA) of transcription regulators. We extracted the matrix of important TRs activated in the \u03b2-cell subpopulation and bi-hormonal-like \u03b2-cells. Based on these TRs and their targets, we built specific regulatory networks for main cell subpopulations. Our data confirmed the transcriptomic heterogeneity of the \u03b2-cell subtype lineage and suggested a mechanism that could account for the differentiation of \u03b2-cell subtypes during pancreas development. We do believe that our findings could be instrumental for understanding the mechanisms that affect the balance of \u03b2-cell subtypes, leading to impaired insulin secretion in type 2 diabetes.<\/jats:p>\n                  <jats:p\/>","DOI":"10.1039\/d4mo00082j","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T05:55:13Z","timestamp":1730699713000},"page":"654-665","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigation of the motif activity of transcription regulators in pancreatic \u03b2-like cell subpopulations differentiated from human induced pluripotent stem cells"],"prefix":"10.1093","volume":"20","author":[{"given":"Eric","family":"Leclerc","sequence":"first","affiliation":[{"name":"CNRS IRL 2820; Laboratory for Integrated Micro Mechatronic Systems, Institute of Industrial Science, University of Tokyo a , 4-6-1 Komaba; Meguro-ku, Tokyo, 153-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikhail","family":"Pachkov","sequence":"additional","affiliation":[{"name":"SIB Swiss Institute of Bioinformatics, Quartier Sorge \u2013 B\u00e2timent Amphip\u00f4le c , 1015 Lausanne, Switzerland"},{"name":"Biozentrum, University of Basel b , Spitalstrasse 41, 4056 Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Morisseau","sequence":"additional","affiliation":[{"name":"CNRS UMR 7338, Laboratoire de Biom\u00e9canique et Bioing\u00e9nierie, Sorbonne universit\u00e9s, Universit\u00e9 de Technologies de Compi\u00e8gne d , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumiya","family":"Tokito","sequence":"additional","affiliation":[{"name":"Department of Chemical System Engineering, Graduate School of Engineering, the University of Tokyo e , 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecile","family":"Legallais","sequence":"additional","affiliation":[{"name":"CNRS UMR 7338, Laboratoire de Biom\u00e9canique et Bioing\u00e9nierie, Sorbonne universit\u00e9s, Universit\u00e9 de Technologies de Compi\u00e8gne d , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0925-0298","authenticated-orcid":false,"given":"Rachid","family":"Jellali","sequence":"additional","affiliation":[{"name":"CNRS UMR 7338, Laboratoire de Biom\u00e9canique et Bioing\u00e9nierie, Sorbonne universit\u00e9s, Universit\u00e9 de Technologies de Compi\u00e8gne d , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Department of Chemical System Engineering, Graduate School of Engineering, the University of Tokyo e , 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amar","family":"Abderrahmani","sequence":"additional","affiliation":[{"name":"Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520, IEMN f , F-59000 Lille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuyuki","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Chemical System Engineering, Graduate School of Engineering, the University of Tokyo e , 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan"},{"name":"CNRS IRL 2820; Laboratory for Integrated Micro Mechatronic Systems, Institute of Industrial Science, University of Tokyo a , 4-6-1 Komaba; Meguro-ku, Tokyo, 153-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,11,4]]},"reference":[{"issue":"4","key":"2026010813063014200_cit1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.3390\/metabo11040218","article-title":"The Plasticity of Pancreatic \u03b2-Cells","volume":"11","author":"Honzawa","year":"2021","journal-title":"Metabolites"},{"key":"2026010813063014200_cit2","doi-asserted-by":"crossref","first-page":"11756","DOI":"10.1038\/ncomms11756","article-title":"Human islets contain four distinct subtypes of \u03b2 cells","volume":"7","author":"Dorrell","year":"2016","journal-title":"Nat. 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Gastroenterol."},{"issue":"5","key":"2026010813063014200_cit6","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.stem.2023.04.002","article-title":"Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes","volume":"30","author":"Hogrebe","year":"2023","journal-title":"Cell Stem Cell"},{"key":"2026010813063014200_cit7","doi-asserted-by":"crossref","first-page":"114481","DOI":"10.1016\/j.addr.2022.114481","article-title":"Type 1 diabetes and engineering enhanced islet transplantation","volume":"189","author":"Jeyagaran","year":"2022","journal-title":"Adv. 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