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Among these are glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), both expressed by L-cells. These hormones play important roles in promoting satiety; however, how they are regulated transcriptionally is not known. ETS variant transcription factor 1 (ETV1) is expressed by L-cells, but its function remains unknown. Here, we examined Etv1 expression in single-cell RNA-sequencing (scRNA-seq) datasets from the mouse small intestine and from organoid cultures. To assess the functional role of ETV1, loss-of-function and overexpression experiments were performed in organoids. Gene expression was subsequently assessed with quantitative PCR and scRNA-seq. Our results confirmed Etv1 enrichment in the L-cell lineage both in vivo and in organoids. Furthermore, mutations in ETV1 led to a decrease in Pyy expression levels with no effect on Gcg levels or on overall cell composition and organoid morphology. Moreover, overexpression of ETV1 led to a modest, but specific, increase in Pyy levels. We thus identified ETV1 as a regulator of Pyy expression, illustrating, for the first time, how specific hormones in the L-cell lineage are transcriptionally regulated.<\/jats:p>","DOI":"10.1242\/dmm.052610","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T09:21:46Z","timestamp":1759742506000},"source":"Crossref","is-referenced-by-count":4,"title":["ETV1 is a key regulator of enteroendocrine PYY production"],"prefix":"10.1242","volume":"18","author":[{"given":"Astrid M.","family":"Baattrup","sequence":"first","affiliation":[{"name":"Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW) 1 , Department of Biomedical Sciences, Faculty of Health and Medical Sciences , , Blegdamsvej 3B, 2200 Copenhagen ,","place":["Denmark"]},{"name":"University of Copenhagen 1 , Department of Biomedical Sciences, Faculty of Health and Medical Sciences , , Blegdamsvej 3B, 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne Terndrup","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Biotech Research and Innovation Center (BRIC), University of Copenhagen 2 , Ole Maal\u00f8es vej 5, 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5967-286X","authenticated-orcid":false,"given":"Stine L.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW) 1 , Department of Biomedical Sciences, Faculty of Health and Medical Sciences , , Blegdamsvej 3B, 2200 Copenhagen ,","place":["Denmark"]},{"name":"University of Copenhagen 1 , Department of Biomedical Sciences, Faculty of Health and Medical Sciences , , Blegdamsvej 3B, 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martti","family":"Maimets","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW) 1 , Department of Biomedical Sciences, Faculty of Health and Medical Sciences , , Blegdamsvej 3B, 2200 Copenhagen ,","place":["Denmark"]},{"name":"University of Copenhagen 1 , Department of Biomedical Sciences, Faculty of Health and Medical Sciences , , Blegdamsvej 3B, 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Gribble","sequence":"additional","affiliation":[{"name":"Institute of Metabolic Science, University of Cambridge 3 , Hills Road, Cambridge CB2 0QQ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Reimann","sequence":"additional","affiliation":[{"name":"Institute of Metabolic Science, University of Cambridge 3 , Hills Road, Cambridge CB2 0QQ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6569-1664","authenticated-orcid":false,"given":"Kim B.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW) 1 , Department of Biomedical Sciences, Faculty of Health and Medical Sciences , , Blegdamsvej 3B, 2200 Copenhagen ,","place":["Denmark"]},{"name":"University of Copenhagen 1 , Department of Biomedical Sciences, Faculty of Health and Medical Sciences , , Blegdamsvej 3B, 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"2025121206333536600_DMM052610C1","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1016\/0016-5085(85)90211-2","article-title":"Human distribution and release of a putative new gut hormone, peptide YY","volume":"89","author":"Adrian","year":"1985","journal-title":"Gastroenterology"},{"key":"2025121206333536600_DMM052610C2","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1038\/s41574-018-0016-2","article-title":"Glucagon-like peptide 1 in health and disease","volume":"14","author":"Andersen","year":"2018","journal-title":"Nat. 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