{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Dolens AC"],"funding":["Stichting Tegen Kanker","Universiteit Gent (UGent)","Fonds Wetenschappelijk Onderzoek (FWO)","European Hematology Association","Fonds Wetenschappelijk Onderzoek","Universiteit Gent","Stichting Tegen Kanker (Fondation Contre le Cancer)"],"pagination":["e49006"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7202205"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["21(5)"],"pubmed_abstract":["γδ and αβ T cells have unique roles in immunity and both originate in the thymus from T-lineage committed precursors through distinct but unclear mechanisms. Here, we show that Notch1 activation is more stringently required for human γδ development compared to αβ-lineage differentiation and performed paired mRNA and miRNA profiling across 11 discrete developmental stages of human T cell development in an effort to identify the potential Notch1 downstream mechanism. Our data suggest that the miR-17-92 cluster is a Notch1 target in immature thymocytes and that miR-17 can restrict BCL11B expression in these Notch-dependent T cell precursors. We show that enforced miR-17 expression promotes human γδ T cell development and, consistently, that BCL11B is absolutely required for αβ but less for γδ T cell development. This study suggests that human γδ T cell development is mediated by a stage-specific Notch-driven negative feedback loop through which miR-17 temporally restricts BCL11B expression and provides functional insights into the developmental role of the disease-associated genes BCL11B and the miR-17-92 cluster in a human context."],"journal":["EMBO reports"],"pubmed_title":["Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development."],"pmcid":["PMC7202205"],"funding_grant_id":["TRTH104"],"pubmed_authors":["Speleman F","De Mulder K","Van der Meulen J","Weening K","Vandekerckhove B","De Medts J","Taghon T","Velghe I","Van Vlierberghe P","Roels J","Dolens AC","Leclercq G","Vandesompele J","Kerre T","Lavaert M","Mestdagh P","Durinck K","Volders PJ","De Preter K"],"additional_accession":[]},"is_claimable":false,"name":"Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development.","description":"γδ and αβ T cells have unique roles in immunity and both originate in the thymus from T-lineage committed precursors through distinct but unclear mechanisms. Here, we show that Notch1 activation is more stringently required for human γδ development compared to αβ-lineage differentiation and performed paired mRNA and miRNA profiling across 11 discrete developmental stages of human T cell development in an effort to identify the potential Notch1 downstream mechanism. Our data suggest that the miR-17-92 cluster is a Notch1 target in immature thymocytes and that miR-17 can restrict BCL11B expression in these Notch-dependent T cell precursors. We show that enforced miR-17 expression promotes human γδ T cell development and, consistently, that BCL11B is absolutely required for αβ but less for γδ T cell development. This study suggests that human γδ T cell development is mediated by a stage-specific Notch-driven negative feedback loop through which miR-17 temporally restricts BCL11B expression and provides functional insights into the developmental role of the disease-associated genes BCL11B and the miR-17-92 cluster in a human context.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 May","modification":"2024-11-13T14:41:00.527Z","creation":"2024-11-13T14:41:00.527Z"},"accession":"S-EPMC7202205","cross_references":{"pubmed":["32255245"],"doi":["10.15252/embr.201949006"]}}