biostudies-literatureMerle CFondation ARC pour la Recherche sur le CancerAgence Nationale de la Recherche (ANR)Worldwide Cancer Research (WCR)Agence Nationale de la RechercheFondation Schlumberger pour l'Education et la Recherche (FSER)Université de Recherche Paris Sciences et LettresFondation Schlumberger pour l'Education et la RechercheUniversité de Recherche Paris Sciences et Lettres (PSL)Worldwide Cancer ResearchEuropean Research CouncilFondation pour la Recherche Médicale (FRM)Fondation pour la Recherche MédicaleFondation ARC pour la Recherche sur le Cancer (ARC)Wellcome Trust2827-2855https://www.ebi.ac.uk/biostudies/studies/S-EPMC12084385biostudies-literatureUnknown44(10)The mammary epithelium derives from multipotent mammary stem cells (MaSCs) that engage into differentiation during embryonic development. However, adult MaSCs maintain the ability to reactivate multipotency in non-physiological contexts. We previously reported that Notch1 activation in committed basal cells triggers a basal-to-luminal cell fate switch in the mouse mammary gland. Here, we report conservation of this mechanism and found that in addition to the mammary gland, constitutive Notch1 signaling induces a basal-to-luminal cell fate switch in adult cells of the lacrimal gland, the salivary gland, and the prostate. Since the lineage transition is progressive in time, we performed single-cell transcriptomic analysis on index-sorted mammary cells at different stages of lineage conversioThe EMBO journalTranscriptional landscapes underlying Notch-induced lineage conversion and plasticity of mammary basal cells.PMC12084385950349ANR-22-CE13-0009FSER2020021111711-LBX-004424-0216ARCPDF12021020003033)ARCPGA2021120004232_4874C19-64-2019-228ANR-21-CE13-0047EQU201903007821Rodrigues CRulands SPourkhalili Langeroudi AFre SMerle CRost FDang YJournot RfalseTranscriptional landscapes underlying Notch-induced lineage conversion and plasticity of mammary basal cells.The mammary epithelium derives from multipotent mammary stem cells (MaSCs) that engage into differentiation during embryonic development. However, adult MaSCs maintain the ability to reactivate multipotency in non-physiological contexts. We previously reported that Notch1 activation in committed basal cells triggers a basal-to-luminal cell fate switch in the mouse mammary gland. Here, we report conservation of this mechanism and found that in addition to the mammary gland, constitutive Notch1 signaling induces a basal-to-luminal cell fate switch in adult cells of the lacrimal gland, the salivary gland, and the prostate. Since the lineage transition is progressive in time, we performed single-cell transcriptomic analysis on index-sorted mammary cells at different stages of lineage conversio2025-01-01T00:00:00Z2025 May2026-05-29T15:31:52.066Z2026-04-08T05:20:18.192ZS-EPMC120843854018602810.1038/s44318-025-00424-1