{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:17:55Z","timestamp":1788495475280,"version":"build-2803163510"},"reference-count":53,"publisher":"The Company of Biologists","issue":"23","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R00HL119638"],"award-info":[{"award-number":["R00HL119638"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32GM153507"],"award-info":[{"award-number":["T32GM153507"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["F31 HL151090"],"award-info":[{"award-number":["F31 HL151090"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["R01HL146478"],"award-info":[{"award-number":["R01HL146478"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science Foundation","award":["URoL EF-2021552"],"award-info":[{"award-number":["URoL EF-2021552"]}]},{"DOI":"10.13039\/100010280","name":"John H. Tietze Foundation Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010280","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Washington"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>How multipotent progenitors give rise to multiple cell types in defined numbers is a central question in developmental biology. Epigenetic switches, acting at single gene loci, can generate extended delays in the activation of lineage-specifying genes and impact lineage decisions and cell type output. Here, we analyzed a timed epigenetic switch controlling expression of mouse Bcl11b, a transcription factor that drives T-cell commitment, but only after a multi-day delay. To investigate roles for this delay in controlling lineage decision making, we analyzed progenitors with a deletion in a distal Bcl11b enhancer, which extends this delay by \u223c3\u2005days. Strikingly, delaying Bcl11b activation reduces T-cell output but enhances innate lymphoid cell (ILC) generation in the thymus by redirecting uncommitted progenitors to the ILC lineages. Mechanistically, delaying Bcl11b activation promoted ILC redirection by enabling upregulation of the ILC-specifying transcription factor PLZF. Despite the upregulation of PLZF, committed ILC progenitors could subsequently express Bcl11b, which is also needed for type 2 ILC differentiation. These results show that epigenetic switches can control the activation timing and order of lineage-specifying genes to modulate cell type numbers and proportions.<\/jats:p>","DOI":"10.1242\/dev.203016","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T08:56:50Z","timestamp":1733821010000},"source":"Crossref","is-referenced-by-count":5,"title":["A timed epigenetic switch balances T and ILC lineage proportions in the thymus"],"prefix":"10.1242","volume":"151","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6140-1949","authenticated-orcid":false,"given":"Nicholas A.","family":"Pease","sequence":"first","affiliation":[{"name":"University of Washington 1 Department of Bioengineering , , Seattle, WA 98105 ,","place":["USA"]},{"name":"Institute for Stem Cell and Regenerative Medicine, University of Washington 2 , Seattle, WA 98105 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn M.","family":"Denecke","sequence":"additional","affiliation":[{"name":"University of Washington 1 Department of Bioengineering , , Seattle, WA 98105 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Chen","sequence":"additional","affiliation":[{"name":"University of Washington 1 Department of Bioengineering , , Seattle, WA 98105 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Habib","family":"Gerges","sequence":"additional","affiliation":[{"name":"University of Pittsburgh 3 Department of Immunology , , Pittsburgh, PA 15213 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6272-6673","authenticated-orcid":false,"given":"Hao Yuan","family":"Kueh","sequence":"additional","affiliation":[{"name":"University of Washington 1 Department of Bioengineering , , Seattle, WA 98105 ,","place":["USA"]},{"name":"Institute for Stem Cell and Regenerative Medicine, University of Washington 2 , Seattle, WA 98105 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"2024121008510207300_DEV203016C1","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.coisb.2019.10.013","article-title":"Order by chance: origins and benefits of stochasticity in immune cell fate control","volume":"18","author":"Abadie","year":"2019","journal-title":"Curr. 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