title: DAZL limits pluripotency, differentiation, and apoptosis in developing primordial germ cells.
abstract: The scarcity of primordial germ cells (PGCs) in the developing mammalian embryo hampers robust biochemical analysis of the processes that underlie early germ cell formation. Here, we demonstrate that DAZL, a germ cell-specific RNA binding protein, is a robust PGC marker during in vitro germ cell development. Using Dazl-GFP reporter ESCs, we demonstrate that DAZL plays a central role in a large mRNA/protein interactive network that blocks the translation of core pluripotency factors, including Sox2 and Sall4, as well as of Suz12, a polycomb family member required for differentiation of pluripotent cells. Thus, DAZL limits both pluripotency and somatic differentiation in nascent PGCs. In addition, we observed that DAZL associates with mRNAs of key Caspases and similarly inhibits their translation. This elegant fail-safe mechanism ensures that, whereas loss of DAZL results in prolonged expression of pluripotency factors, teratoma formation is avoided due to the concomitant activation of the apoptotic cascade.
authors.affiliation: Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Hsu-Hsin
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Hubrecht Institute and University Medical Center, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Maaike
authors.initials: M
authors.lastname: Welling
authors.affiliation: Department of Rheumatology, Allergy and Immunology, Department of Rheumatology, Center for Immunology and Inflammatory Diseases, Boston, MA 02114, USA.
authors.forename: Donald B
authors.initials: DB
authors.lastname: Bloch
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences and Netherlands Proteomics Center, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors.forename: Javier
authors.initials: J
authors.lastname: Muñoz
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, 3000 CA Rotterdam, the Netherlands.
authors.forename: Edwin
authors.initials: E
authors.lastname: Mientjes
authors.affiliation: Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical College, Guangzhou 510150, PR China.
authors.forename: Xinjie
authors.initials: X
authors.lastname: Chen
authors.affiliation: Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Cody
authors.initials: C
authors.lastname: Tramp
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yabuuchi
authors.affiliation: Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Chou
authors.affiliation: Hubrecht Institute and University Medical Center, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Christa
authors.initials: C
authors.lastname: Buecker
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Krainer
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, 3000 CA Rotterdam, the Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Willemsen
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences and Netherlands Proteomics Center, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Heck
authors.affiliation: Hubrecht Institute and University Medical Center, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Department of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM Utrecht, the Netherlands. Electronic address: n.geijsen@hubrecht.eu.
authors.forename: Niels
authors.initials: N
authors.lastname: Geijsen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D005854:Germ Cells / Q000378:metabolism*; D015151:Immunoblotting; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D020411:Oligonucleotide Array Sequence Analysis; D039904:Pluripotent Stem Cells / Q000378:metabolism; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C508515:DAZL protein, mouse; D008164:Luminescent Proteins; D016601:RNA-Binding Proteins