@article{59e360bc8619442fa4b454a62b21ff5e,
title = "Inhibition of pluripotency networks by the Rb tumor suppressor restricts reprogramming and tumorigenesis",
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.",
author = "Kareta, {Michael S.} and Gorges, {Laura L.} and Sana Hafeez and Benayoun, {B{\'e}r{\'e}nice A.} and Samuele Marro and Zmoos, {Anne Flore} and Cecchini, {Matthew J.} and Damek Spacek and Batista, {Luis F.Z.} and Megan O'Brien and Ng, {Yi Han} and Ang, {Cheen Euong} and Dedeepya Vaka and Artandi, {Steven E.} and Dick, {Frederick A.} and Anne Brunet and Julien Sage and Marius Wernig",
note = "Funding Information: We would like to thank Gary Mantalas, Ben Passarelli, and Steven Quake for sequencing; Helen Blau for critical reading of the manuscript; Moritz Mall for the CRISPR vectors; and Jamie Imam for assistance with teratoma assays. This work was supported by PHS Grant #T32 CA09151, awarded by the NCI; DHHS (M.S.K.); the Spectrum Child Health Child Health Research Institute (M.S.K.); CIHR MD/PhD (M.J.C.); the Lucile Packard Foundation for Children{\textquoteright}s Health (J.S.); and the CIRM (CIRM RB1-01385 - J.S.). F.A.D. is the Wolfe Senior Fellow in Tumor Suppressor Genes at Western University, M.W. is a New York Stem Cell Foundation-Robertson Investigator and a Tashia and John Morgridge Faculty Scholar, and J.S. is the Harriet and Mary Zelencik Scientist in Children{\textquoteright}s Cancer and Blood Diseases. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = jan,
day = "8",
doi = "10.1016/j.stem.2014.10.019",
language = "English",
volume = "16",
pages = "39--50",
journal = "Cell Stem Cell",
issn = "1934-5909",
number = "1",
}