Netrin-1 regulates somatic cell reprogramming and pluripotency maintenance
| Autor: | Duygu Ozmadenci, Nicolas Gadot, Agnès Bernet, Annelise Bennaceur-Griscelli, Isabelle Durand, Olivier Feraud, Jian Ge, Hongkui Deng, Elsa Kress, Fabrice Lavial, Benjamin Ducarouge, Michela Plateroti, Jesús Gil, Benjamin Gibert, Patrick Mehlen, Jean-Yves Scoazec, Suzy Markossian |
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| Přispěvatelé: | Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut interdisciplinaire d'anthropologie du contemporain (IIAC), École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire Central d'Anatomie et de Cytologie Pathologiques [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Cell Proliferation Group, Imperial College London, Apoptose Cancer et Développement, Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut cellule souche et cerveau (U846 Inserm - UCBL1), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), Institut cellule souche et cerveau (SBRI), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Pluripotent Stem Cells
animal structures General Physics and Astronomy Receptors Cell Surface [SDV.BC]Life Sciences [q-bio]/Cellular Biology [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Biology General Biochemistry Genetics and Molecular Biology Article Kruppel-Like Factor 4 Mice SOX2 Netrin Animals Humans Nerve Growth Factors Induced pluripotent stem cell Promoter Regions Genetic Cells Cultured ComputingMilieux_MISCELLANEOUS Induced stem cells Multidisciplinary Tumor Suppressor Proteins fungi General Chemistry Fibroblasts Netrin-1 Cellular Reprogramming Embryonic stem cell Mi-2/NuRD complex Recombinant Proteins 3. Good health Cell biology Gene Expression Regulation KLF4 embryonic structures Netrin Receptors Reprogramming Signal Transduction |
| Zdroj: | Nature Communications Nature Communications, Nature Publishing Group, 2015, 6 (1), ⟨10.1038/ncomms8398⟩ Nature Communications, 2015, 6 (1), ⟨10.1038/ncomms8398⟩ |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms8398⟩ |
| Popis: | The generation of induced pluripotent stem (iPS) cells holds great promise in regenerative medicine. The use of the transcription factors Oct4, Sox2, Klf4 and c-Myc for reprogramming is extensively documented, but comparatively little is known about soluble molecules promoting reprogramming. Here we identify the secreted cue Netrin-1 and its receptor DCC, described for their respective survival/death functions in normal and oncogenic contexts, as reprogramming modulators. In various somatic cells, we found that reprogramming is accompanied by a transient transcriptional repression of Netrin-1 mediated by an Mbd3/Mta1/Chd4-containing NuRD complex. Mechanistically, Netrin-1 imbalance induces apoptosis mediated by the receptor DCC in a p53-independent manner. Correction of the Netrin-1/DCC equilibrium constrains apoptosis and improves reprogramming efficiency. Our work also sheds light on Netrin-1's function in protecting embryonic stem cells from apoptosis mediated by its receptor UNC5b, and shows that the treatment with recombinant Netrin-1 improves the generation of mouse and human iPS cells. Reprogramming holds great promise for regenerative medicine but the molecular mechanisms governing the generation of induced pluripotent stem cells remain unclear. Here, the authors reveal functions for the axonal guidance cue Netrin-1 in constraining apoptosis at the early stage of reprogramming and in established pluripotent cells. |
| Databáze: | OpenAIRE |
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