{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:43:13Z","timestamp":1791247393539,"version":"4.1.0"},"reference-count":45,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,5,15]]},"abstract":"<jats:p>Hematopoietic stem cells (HSCs) sustain lifelong production of all blood cell types through finely balanced divisions leading to self-renewal and differentiation. Although several genes influencing HSC self-renewal have been identified, to date no gene has been described that, when activated, enhances HSC self-renewal and, when activated, promotes HSC differentiation. We observe that the retinoic acid receptor (RAR)\u03b3 is selectively expressed in primitive hematopoietic precursors and that the bone marrow of RAR\u03b3 knockout mice exhibit markedly reduced numbers of HSCs associated with increased numbers of more mature progenitor cells compared with wild-type mice. In contrast, RAR\u03b1 is widely expressed in hematopoietic cells, but RAR\u03b1 knockout mice do not exhibit any HSC or progenitor abnormalities. Primitive hematopoietic precursors overexpressing RAR\u03b1 differentiate predominantly to granulocytes in short-term culture, whereas those overexpressing RAR\u03b3 exhibit a much more undifferentiated phenotype. Furthermore, loss of RAR\u03b3 abrogated the potentiating effects of all-trans retinoic acid on the maintenance of HSCs in ex vivo culture. Finally, pharmacological activation of RAR\u03b3 ex vivo promotes HSC self-renewal, as demonstrated by serial transplant studies. We conclude that the RARs have distinct roles in hematopoiesis and that RAR\u03b3 is a critical physiological and pharmacological regulator of the balance between HSC self-renewal and differentiation.<\/jats:p>","DOI":"10.1084\/jem.20052105","type":"journal-article","created":{"date-parts":[[2006,5,8]],"date-time":"2006-05-08T21:40:40Z","timestamp":1147124440000},"page":"1283-1293","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":188,"title":["RAR\u03b3 is critical for maintaining a balance between hematopoietic stem cell self-renewal and differentiation"],"prefix":"10.1084","volume":"203","author":[{"given":"Louise E.","family":"Purton","sequence":"first","affiliation":[{"name":"1Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Dworkin","sequence":"additional","affiliation":[{"name":"1Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma Haines","family":"Olsen","sequence":"additional","affiliation":[{"name":"1Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl R.","family":"Walkley","sequence":"additional","affiliation":[{"name":"1Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia"},{"name":"2Department of Medicine, University of Melbourne, Fitzroy, Victoria 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stewart A.","family":"Fabb","sequence":"additional","affiliation":[{"name":"1Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Collins","sequence":"additional","affiliation":[{"name":"3Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Chambon","sequence":"additional","affiliation":[{"name":"4Institut de Ge\u0301ne\u0301tique et de Biologie Mole\u0301culaire et Cellulaire, Centre National de la Recherche Scientifique\/Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale\/ULP\/Colle\u0300ge de France, 67404 Illkirch Cedex, CU de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2006,5,8]]},"reference":[{"key":"2023072513361138000_BIB1","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1101\/gad.9.14.1753","volume":"9","year":"1995","journal-title":"Genes Dev."},{"key":"2023072513361138000_BIB2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0092-8674(02)00697-9","volume":"109","year":"2002","journal-title":"Cell."},{"key":"2023072513361138000_BIB3","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1038\/81390","volume":"6","year":"2000","journal-title":"Nat. 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