Title |
Inhibition of Pluripotency Networks by the Rb Tumor Suppressor Restricts Reprogramming and Tumorigenesis
|
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Published in |
Cell Stem Cell, November 2014
|
DOI | 10.1016/j.stem.2014.10.019 |
Pubmed ID | |
Authors |
Michael S. Kareta, Laura L. Gorges, Sana Hafeez, Bérénice A. Benayoun, Samuele Marro, Anne-Flore Zmoos, Matthew J. Cecchini, Damek Spacek, Luis F.Z. Batista, Megan O’Brien, Yi-Han Ng, Cheen Euong Ang, Dedeepya Vaka, Steven E. Artandi, Frederick A. Dick, Anne Brunet, Julien Sage, Marius Wernig |
Abstract |
Mutations in the retinoblastoma tumor suppressor gene Rb are involved in many forms of human cancer. In this study, we investigated the early consequences of inactivating Rb in the context of cellular reprogramming. We found that Rb inactivation promotes the reprogramming of differentiated cells to a pluripotent state. Unexpectedly, this effect is cell cycle independent, and instead reflects direct binding of Rb to pluripotency genes, including Sox2 and Oct4, which leads to a repressed chromatin state. More broadly, this regulation of pluripotency networks and Sox2 in particular is critical for the initiation of tumors upon loss of Rb in mice. These studies therefore identify Rb as a global transcriptional repressor of pluripotency networks, providing a molecular basis for previous reports about its involvement in cell fate pliability, and implicate misregulation of pluripotency factors such as Sox2 in tumorigenesis related to loss of Rb function. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 4 | 14% |
France | 2 | 7% |
Germany | 2 | 7% |
Australia | 1 | 4% |
Japan | 1 | 4% |
Austria | 1 | 4% |
Saudi Arabia | 1 | 4% |
India | 1 | 4% |
United Kingdom | 1 | 4% |
Other | 1 | 4% |
Unknown | 13 | 46% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 17 | 61% |
Scientists | 7 | 25% |
Science communicators (journalists, bloggers, editors) | 4 | 14% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Spain | 2 | <1% |
United States | 2 | <1% |
Japan | 2 | <1% |
United Kingdom | 1 | <1% |
Portugal | 1 | <1% |
France | 1 | <1% |
Korea, Republic of | 1 | <1% |
Unknown | 223 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 66 | 28% |
Researcher | 47 | 20% |
Student > Master | 30 | 13% |
Student > Bachelor | 13 | 6% |
Professor > Associate Professor | 12 | 5% |
Other | 33 | 14% |
Unknown | 32 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 82 | 35% |
Agricultural and Biological Sciences | 72 | 31% |
Medicine and Dentistry | 26 | 11% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 2% |
Immunology and Microbiology | 3 | 1% |
Other | 14 | 6% |
Unknown | 32 | 14% |