{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Pereira MSF"],"funding":["Nationwide Children's Hospital","NIH HHS"],"pagination":["705"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9913837"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(3)"],"pubmed_abstract":["Loss of cytotoxicity and defective metabolism are linked to glycogen synthase kinase 3 beta (GSK3β) overexpression in natural killer (NK) cells from patients with acute myeloid leukemia or from healthy donors after expansion ex vivo with IL-15. Drug inhibition of GSK3β in these NK cells improves their maturation and cytotoxic activity, but the mechanisms of GSK3β-mediated dysfunction have not been well studied. Here, we show that expansion of NK cells with feeder cells expressing membrane-bound IL-21 maintained normal GSK3β levels, allowing us to study GSK3β function using CRISPR gene editing. We deleted <i>GSK3B</i> and expanded paired-donor knockout and wild-type (WT) NK cells and then assessed transcriptional and functional alterations induced by loss of GSK3β. Surprisingly, our data sh"],"journal":["Cancers"],"pubmed_title":["Deletion of Glycogen Synthase Kinase 3 Beta Reprograms NK Cell Metabolism."],"pmcid":["PMC9913837"],"funding_grant_id":["AWD00001042","U54-CA232561"],"pubmed_authors":["Maguire C","Naeimi Kararoudi M","Mundy-Bosse BL","Sorathia K","Thakkar A","Lee DA","Collins PL","Pereira MSF","Sezgin Y"],"additional_accession":[]},"is_claimable":false,"name":"Deletion of Glycogen Synthase Kinase 3 Beta Reprograms NK Cell Metabolism.","description":"Loss of cytotoxicity and defective metabolism are linked to glycogen synthase kinase 3 beta (GSK3β) overexpression in natural killer (NK) cells from patients with acute myeloid leukemia or from healthy donors after expansion ex vivo with IL-15. Drug inhibition of GSK3β in these NK cells improves their maturation and cytotoxic activity, but the mechanisms of GSK3β-mediated dysfunction have not been well studied. Here, we show that expansion of NK cells with feeder cells expressing membrane-bound IL-21 maintained normal GSK3β levels, allowing us to study GSK3β function using CRISPR gene editing. We deleted <i>GSK3B</i> and expanded paired-donor knockout and wild-type (WT) NK cells and then assessed transcriptional and functional alterations induced by loss of GSK3β. Surprisingly, our data sh","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2025-04-25T19:25:01.9Z","creation":"2025-04-06T07:57:57.024Z"},"accession":"S-EPMC9913837","cross_references":{"pubmed":["36765663"],"doi":["10.3390/cancers15030705"]}}