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ABSTRACT Replying to: H. F. Jørgensen, Z.-F. Chen, M. Merkenschlager & A. G. Fisher _Nature_ 457, 10.1038/nature07783; N. J. Buckley, R. Johnson, Y.-M. Sun & L. W. Stanton _Nature_
457, 10.1038/nature07784 (2009) In contrast to the comments made by Jørgensen _et al._1 and Buckley _et al._2, our experiments showed that REST maintains the self-renewal and pluripotency of
mouse embryonic stem cells (mESCs)3. Two recent papers support our work: ref. 4 indicated that REST is indeed in the network that regulates ESC self-renewal and pluripotency and ref. 5
showed that mESCs with lower REST levels derived from a mouse model of Down’s syndrome have decreased levels of self-renewal markers and a higher propensity towards differentiation, even
when cultured in the presence of LIF. We note that Buckley and Stanton also recently concluded that REST is part of the Oct4–Sox2–Nanog regulatory network and has “a key role in the
maintenance of the ESC phenotype”6. We proposed that REST represses a set of microRNAs that potentially target self-renewal genes. At least one of them, miR-21, represses self-renewal,
probably by destabilizing the messenger RNAs of Sox2 and/or Nanog (not Tbx3 or c-Myc as suggested by Buckley _et al._2). In this model, changes in the cellular environment that counter this
function of REST or stimulate the mRNA levels of Sox2 or Nanog could minimize the effect of REST. For this reason, in our study we used mESCs with a low passage number, and we cultured them
without feeder cells to avoid possible contributions of the feeder cells or an adaptive response to high passage. Access through your institution Buy or subscribe This is a preview of
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CRISPR-CAS9 SCREENS UNCOUPLE HUMAN PLURIPOTENT STEM CELL IDENTITY VERSUS FITNESS Article Open access 17 October 2024 DUSP6 IS A MEMORY RETENTION FEEDBACK REGULATOR OF ERK SIGNALING FOR
CELLULAR RESILIENCE OF HUMAN PLURIPOTENT STEM CELLS IN RESPONSE TO DISSOCIATION Article Open access 07 April 2023 A RETINOID ANALOGUE, TTNPB, PROMOTES CLONAL EXPANSION OF HUMAN PLURIPOTENT
STEM CELLS BY UPREGULATING _CLDN2_ AND _HOXA1_ Article Open access 16 February 2024 REFERENCES * Jørgensen, H. F., Chen, Z.-F., Merkenschlager, M. & Fisher, A. G. Is REST required for
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address: Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California 92037, USA AUTHORS AND AFFILIATIONS * Department of Genetics, The University of Texas M. D.
Anderson Cancer Center, Houston, 77030, Texas, USA Sanjay K. Singh, Mohamedi N. Kagalwala, Henry Adams & Sadhan Majumder * Department of Biochemistry and Molecular Biology, The
University of Texas M. D. Anderson Cancer Center, Houston, 77030, Texas, USA Jan Parker-Thornburg * Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center,
Houston, 77030, Texas, USA Sadhan Majumder * The Brain Tumor Center, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, Texas, USA Sadhan Majumder * Center for Stem Cell
and Developmental Biology, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, Texas, USA Sanjay K. Singh, Mohamedi N. Kagalwala & Sadhan Majumder * Program in Genes
and Development, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, 77030, Texas, USA Sadhan Majumder Authors * Sanjay K. Singh View author publications You
can also search for this author inPubMed Google Scholar * Mohamedi N. Kagalwala View author publications You can also search for this author inPubMed Google Scholar * Jan Parker-Thornburg
View author publications You can also search for this author inPubMed Google Scholar * Henry Adams View author publications You can also search for this author inPubMed Google Scholar *
Sadhan Majumder View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE
Singh, S., Kagalwala, M., Parker-Thornburg, J. _et al._ _Singh_ et al. _reply_. _Nature_ 457, E7 (2009). https://doi.org/10.1038/nature07785 Download citation * Issue Date: 26 February 2009
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