title: Mga is essential for the survival of pluripotent cells during peri-implantation development.
abstract: The maintenance and control of pluripotency is of great interest in stem cell biology. The dual specificity T-box/basic-helix-loop-helix-zipper transcription factor Mga is expressed in the pluripotent cells of the inner cell mass (ICM) and epiblast of the peri-implantation mouse embryo, but its function has not been investigated previously. Here, we use a loss-of-function allele and RNA knockdown to demonstrate that Mga depletion leads to the death of proliferating pluripotent ICM cells in vivo and in vitro, and the death of embryonic stem cells (ESCs) in vitro. Additionally, quiescent pluripotent cells lacking Mga are lost during embryonic diapause. Expression of Odc1, the rate-limiting enzyme in the conversion of ornithine into putrescine in the synthesis of polyamines, is reduced in Mga mutant cells, and the survival of mutant ICM cells as well as ESCs is rescued in culture by the addition of exogenous putrescine. These results suggest a mechanism whereby Mga influences pluripotent cell survival through regulation of the polyamine pool in pluripotent cells of the embryo, whether they are in a proliferative or quiescent state.
authors.affiliation: Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Washkowitz
authors.affiliation: Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Schall
authors.affiliation: Department of Veterinary and Animal Science, University of Massachusetts, Amherst, Amherst, MA 01003, USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München - German Research Center for Environmental Health, Technical University of München, 85764 Neuherberg, Germany Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), Standort München, and Munich Cluster for Systems Neurology (SyNergy), Adolf-Butenandt-Institut, Ludwig-Maximilians-Universität München, 80336 München, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München - German Research Center for Environmental Health, Technical University of München, 85764 Neuherberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Floss
authors.affiliation: Department of Veterinary and Animal Science, University of Massachusetts, Amherst, Amherst, MA 01003, USA.
authors.forename: Jesse
authors.initials: J
authors.lastname: Mager
authors.affiliation: Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA vep1@columbia.edu.
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Papaioannou
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins; D053624:Blastocyst Inner Cell Mass / Q000166:cytology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D003433:Crosses, Genetic; D010064:Embryo Implantation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D018390:Gene Targeting; D005838:Genotype; D005855:Germ Layers / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D016296:Mutagenesis / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009955:Ornithine Decarboxylase / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009955:Ornithine Decarboxylase; D011073:Polyamines; D014157:Transcription Factors; C403042:Mga protein, mouse
keywords: Basic-helix-loop-helix-zipper; ESCs; Mga; Mouse; ODC; Pluripotency; T-box; Transcription factor