{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:30:54Z","timestamp":1786437054678,"version":"build-2736575974"},"reference-count":148,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["EP\/Y030818\/1"],"award-info":[{"award-number":["EP\/Y030818\/1"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]},{"award":["EP\/Y030818\/1"],"award-info":[{"award-number":["EP\/Y030818\/1"]}],"id":[{"id":"https:\/\/ror.org\/001aqnf71","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>RAR\u03b3 is expressed during embryogenesis by stem\/primitive progenitor cells, indicating a role in controlling their development. Supporting this view is that a physiological level of 10 nM of the RAR\u03b3 agonist AGN205327 blocked stem\/progenitor cell differentiation during zebrafish embryogenesis, mouse gastruloid development, and adult chondro- and osteogenesis. Similarly, transgene expression of RAR\u03b3 or the use of the RAR\u03b3 agonist CD437 enhanced the generation of induced pluripotent stem cells (iPSCs) from human and mouse somatic cells. RAR\u03b3 regulates many events that control the behavior of stem\/progenitor cells regarding whether they develop to give rise to mature cells. RAR\u03b3 positively regulates the expressions of NOTCH ligands and their receptors, transforming growth factors (TGFs), and molecules pertaining to cell identity, extracellular matrix communication, and all-trans retinoic acid synthesis and catabolism. The genes that are repressed by RAR\u03b3 include RAR\u03b3, PPAR\u03b3, and RXR\u03b1. RAR\u03b3 integrates into Wnt\/\u03b2-catenin and TGF\u03b2 signaling by acting as a co-factor to the gene co-activator \u03b2-catenin and transcription factor Smad3, respectively. Within the cytoplasm, RAR\u03b3 regulates Akt\/NF-\u03baB signaling. As a model, we propose that ATRA ligand-activated RAR\u03b3 acts as a gatekeeper to stem cell developmental progression during embryogenesis and that this role extends to stem\/progenitor cell homeostasis within adult tissues.<\/jats:p>","DOI":"10.3390\/ijms27167160","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:09:36Z","timestamp":1786435776000},"page":"7160","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Retinoic Acid Receptor \u03b3 Is a Ligand-Activated Gatekeeper to Stem Cell Developmental Progression"],"prefix":"10.3390","volume":"27","author":[{"given":"William Eustace Basil","family":"Johnson","sequence":"first","affiliation":[{"name":"Chester Medical School, University of Chester, Chester CH1 4B1, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7674-3797","authenticated-orcid":false,"given":"Caitlin","family":"McQueen","sequence":"additional","affiliation":[{"name":"Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0821-0275","authenticated-orcid":false,"given":"Geoffrey","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Medicine and Health, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1096\/fasebj.10.9.8801176","article-title":"A decade of molecular biology of retinoic acid receptors","volume":"10","author":"Chambon","year":"1996","journal-title":"FASEB J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"T13","DOI":"10.1530\/JME-22-0097","article-title":"Retinoic acid receptors at 35 years","volume":"69","author":"Petkovich","year":"2022","journal-title":"J. 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