{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bone HK"],"funding":["Medical Research Council","Wellcome Trust","Engineering and Physical Sciences Research Council"],"pagination":["1992-2000"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3104033"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["124(Pt 12)"],"pubmed_abstract":["The use of small molecules to 'chemically direct' differentiation represents a powerful approach to promote specification of embryonic stem cells (ESCs) towards particular functional cell types for use in regenerative medicine and pharmaceutical applications. Here, we demonstrate a novel route for chemically directed differentiation of human ESCs (hESCs) into definitive endoderm (DE) exploiting a selective small-molecule inhibitor of glycogen synthase kinase 3 (GSK-3). This GSK-3 inhibitor, termed 1m, when used as the only supplement to a chemically defined feeder-free culture system, effectively promoted differentiation of ESC lines towards primitive streak (PS), mesoderm and DE. This contrasts with the role of GSK-3 in murine ESCs, where GSK-3 inhibition promotes pluripotency. Interestingly, 1m-mediated induction of differentiation involved transient NODAL expression and Nodal signalling. Prolonged treatment of hESCs with 1m resulted in the generation of a population of cells displaying hepatoblast characteristics, that is expressing α-fetoprotein and HNF4α. Furthermore, 1m-induced DE had the capacity to mature and generate hepatocyte-like cells capable of producing albumin. These findings describe, for the first time, the utility of GSK-3 inhibition, in a chemically directed approach, to a method of DE generation that is robust, potentially scalable and applicable to different hESC lines."],"journal":["Journal of cell science"],"pubmed_title":["A novel chemically directed route for the generation of definitive endoderm from human embryonic stem cells based on inhibition of GSK-3."],"pmcid":["PMC3104033"],"funding_grant_id":["GR/S99419/01","MC_G1000732"],"pubmed_authors":["Nelson AS","Goldring CE","Tosh D","Welham MJ","Bone HK"],"additional_accession":[]},"is_claimable":false,"name":"A novel chemically directed route for the generation of definitive endoderm from human embryonic stem cells based on inhibition of GSK-3.","description":"The use of small molecules to 'chemically direct' differentiation represents a powerful approach to promote specification of embryonic stem cells (ESCs) towards particular functional cell types for use in regenerative medicine and pharmaceutical applications. Here, we demonstrate a novel route for chemically directed differentiation of human ESCs (hESCs) into definitive endoderm (DE) exploiting a selective small-molecule inhibitor of glycogen synthase kinase 3 (GSK-3). This GSK-3 inhibitor, termed 1m, when used as the only supplement to a chemically defined feeder-free culture system, effectively promoted differentiation of ESC lines towards primitive streak (PS), mesoderm and DE. This contrasts with the role of GSK-3 in murine ESCs, where GSK-3 inhibition promotes pluripotency. Interestingly, 1m-mediated induction of differentiation involved transient NODAL expression and Nodal signalling. Prolonged treatment of hESCs with 1m resulted in the generation of a population of cells displaying hepatoblast characteristics, that is expressing α-fetoprotein and HNF4α. Furthermore, 1m-induced DE had the capacity to mature and generate hepatocyte-like cells capable of producing albumin. These findings describe, for the first time, the utility of GSK-3 inhibition, in a chemically directed approach, to a method of DE generation that is robust, potentially scalable and applicable to different hESC lines.","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Jun","modification":"2025-04-22T08:48:10.902Z","creation":"2019-03-27T00:42:06Z"},"accession":"S-EPMC3104033","cross_references":{"pubmed":["21610099"],"doi":["10.1242/jcs.081679"]}}