title: Co-existence of intact stemness and priming of neural differentiation programs in mES cells lacking Trim71.
abstract: Regulatory networks for differentiation and pluripotency in embryonic stem (ES) cells have long been suggested to be mutually exclusive. However, with the identification of many new components of these networks ranging from epigenetic, transcriptional, and translational to even post-translational mechanisms, the cellular states of pluripotency and early differentiation might not be strictly bi-modal, but differentiating stem cells appear to go through phases of simultaneous expression of stemness and differentiation genes. Translational regulators such as RNA binding proteins (RBPs) and micro RNAs (miRNAs) might be prime candidates for guiding a cell from pluripotency to differentiation. Using Trim71, one of two members of the Tripartite motif (Trim) protein family with RNA binding activity expressed in murine ES cells, we demonstrate that Trim71 is not involved in regulatory networks of pluripotency but regulates neural differentiation. Loss of Trim71 in mES cells leaves stemness and self-maintenance of these cells intact, but many genes required for neural development are up-regulated at the same time. Concordantly, Trim71(-/-) mES show increased neural marker expression following treatment with retinoic acid. Our findings strongly suggest that Trim71 keeps priming steps of differentiation in check, which do not pre-require a loss of the pluripotency network in ES cells.
authors.affiliation: Molecular Immunology and Cell Biology, Life and Medical Sciences Institute, University of Bonn, Bonn,Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Mitschka
authors.affiliation: Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ulas
authors.affiliation: Molecular Immunology and Cell Biology, Life and Medical Sciences Institute, University of Bonn, Bonn,Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Goller
authors.affiliation: Molecular Immunology and Cell Biology, Life and Medical Sciences Institute, University of Bonn, Bonn,Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Schneider
authors.affiliation: Department of Developmental Pathology, Institute of Pathology, University of Bonn Medical School, Bonn, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Egert
authors.affiliation: Institute for Reconstructive Neurobiology, Life and Brain Center, University of Bonn and Hertie Foundation, Bonn, Germany.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Mertens
authors.affiliation: Institute for Reconstructive Neurobiology, Life and Brain Center, University of Bonn and Hertie Foundation, Bonn, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Brüstle
authors.affiliation: Department of Developmental Pathology, Institute of Pathology, University of Bonn Medical School, Bonn, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Schorle
authors.affiliation: Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Beyer
authors.affiliation: Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Klee
authors.affiliation: Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Jia
authors.initials: J
authors.lastname: Xue
authors.affiliation: Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Günther
authors.affiliation: Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Kevin
authors.initials: K
authors.lastname: Bassler
authors.affiliation: Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
authors.affiliation: Molecular Immunology and Cell Biology, Life and Medical Sciences Institute, University of Bonn, Bonn,Germany.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Kolanus
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D051379:Mice; D054258:Neural Plate / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D020413:3' Untranslated Regions; C511366:LIN-41 protein, mouse; D014157:Transcription Factors