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Netrin-1 regulates somatic cell reprogramming and pluripotency maintenance

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Title: Netrin-1 regulates somatic cell reprogramming and pluripotency maintenance
Authors: Ozmadenci, D
Féraud, O
Markossian, S
Kress, E
Ducarouge, B
Gibert, B
Ge, J
Durand, I
Gadot, N
Plateroti, M
Bennaceur-Griscelli, A
Scoazec, JY
Gil, J
Deng, H
Bernet, A
Mehlen, P
Lavial, F
Item Type: Journal Article
Abstract: 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-1s 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.
Issue Date: 8-Jul-2015
Date of Acceptance: 5-May-2015
URI: http://hdl.handle.net/10044/1/25733
DOI: https://dx.doi.org/10.1038/ncomms8398
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 6
Copyright Statement: © 2015, Rights Managed by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Publication Status: Published
Article Number: 7398
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine



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