title: MUC1* ligand, NM23-H1, is a novel growth factor that maintains human stem cells in a more naïve state.
abstract: We report that a single growth factor, NM23-H1, enables serial passaging of both human ES and iPS cells in the absence of feeder cells, their conditioned media or bFGF in a fully defined xeno-free media on a novel defined, xeno-free surface. Stem cells cultured in this system show a gene expression pattern indicative of a more "naïve" state than stem cells grown in bFGF-based media. NM23-H1 and MUC1* growth factor receptor cooperate to control stem cell self-replication. By manipulating the multimerization state of NM23-H1, we override the stem cell's inherent programming that turns off pluripotency and trick the cells into continuously replicating as pluripotent stem cells. Dimeric NM23-H1 binds to and dimerizes the extra cellular domain of the MUC1* transmembrane receptor which stimulates growth and promotes pluripotency. Inhibition of the NM23-H1/MUC1* interaction accelerates differentiation and causes a spike in miR-145 expression which signals a cell's exit from pluripotency.
authors.affiliation: Minerva Biotechnologies, Waltham, Massachusetts, United States of America.
authors.forename: Benoit J
authors.initials: BJ
authors.lastname: Smagghe
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Stewart
authors.forename: Mark G
authors.initials: MG
authors.lastname: Carter
authors.forename: Laura M
authors.initials: LM
authors.lastname: Shelton
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Bernier
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Hartman
authors.forename: Amy K
authors.initials: AK
authors.lastname: Calhoun
authors.forename: Vasilios M
authors.initials: VM
authors.lastname: Hatziioannou
authors.forename: Gabriele
authors.initials: G
authors.lastname: Lillacci
authors.forename: Brian A
authors.initials: BA
authors.lastname: Kirk
authors.forename: Brian A
authors.initials: BA
authors.lastname: DiNardo
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kosik
authors.forename: Cynthia
authors.initials: C
authors.lastname: Bamdad
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001667:Binding, Competitive; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D018396:Mucin-1 / Q000276:immunology / Q000378:metabolism; D054778:NM23 Nucleoside Diphosphate Kinases / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D055503:Protein Multimerization; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D017077:Culture Media, Conditioned; D008024:Ligands; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D018396:Mucin-1; D054778:NM23 Nucleoside Diphosphate Kinases; D016222:Fibroblast Growth Factor 2