TITLE

Ago2 Immunoprecipitation Identifies Predicted MicroRNAs in Human Embryonic Stem Cells and Neural Precursors

AUTHOR(S)
Goff, Loyal A.; Davila, Jonathan; Swerdel, Mavis R.; Moore, Jennifer C.; Cohen, Rick I.; Hao Wu; Sun, Yi E.; Hart, Ronald P.
PUB. DATE
September 2009
SOURCE
PLoS ONE;2009, Vol. 4 Issue 9, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: MicroRNAs are required for maintenance of pluripotency as well as differentiation, but since more microRNAs have been computationally predicted in genome than have been found, there are likely to be undiscovered microRNAs expressed early in stem cell differentiation. Methodology/Principal Findings: SOLiD ultra-deep sequencing identified .107 unique small RNAs from human embryonic stem cells (hESC) and neural-restricted precursors that were fit to a model of microRNA biogenesis to computationally predict 818 new microRNA genes. These predicted genomic loci are associated with chromatin patterns of modified histones that are predictive of regulated gene expression. 146 of the predicted microRNAs were enriched in Ago2-containing complexes along with 609 known microRNAs, demonstrating association with a functional RISC complex. This Ago2 IP-selected subset was consistently expressed in four independent hESC lines and exhibited complex patterns of regulation over development similar to previously-known microRNAs, including pluripotency-specific expression in both hESC and iPS cells. More than 30% of the Ago2 IP-enriched predicted microRNAs are new members of existing families since they share seed sequences with known microRNAs. Conclusions/Significance: Extending the classic definition of microRNAs, this large number of new microRNA genes, the majority of which are less conserved than their canonical counterparts, likely represent evolutionarily recent regulators of early differentiation. The enrichment in Ago2 containing complexes, the presence of chromatin marks indicative of regulated gene expression, and differential expression over development all support the identification of 146 new microRNAs active during early hESC differentiation.
ACCESSION #
55980510

 

Related Articles

  • SNF5 Is an Essential Executor of Epigenetic Regulation during Differentiation. Jueng Soo You; De Carvalho, Daniel D.; Chao Dai; Minmin Liu; Pandiyan, Kurinji; Zhou, Xianghong J.; Gangning Liang; Jones, Peter A. // PLoS Genetics;Apr2013, Vol. 9 Issue 4, Special section p1 

    Nucleosome occupancy controls the accessibility of the transcription machinery to DNA regulatory regions and serves an instructive role for gene expression. Chromatin remodelers, such as the BAF complexes, are responsible for establishing nucleosome occupancy patterns, which are key to...

  • Enhancer decommissioning by LSD1 during embryonic stem cell differentiation. Whyte, Warren A.; Bilodeau, Steve; Orlando, David A.; Hoke, Heather A.; Frampton, Garrett M.; Foster, Charles T.; Cowley, Shaun M.; Young, Richard A. // Nature;2/9/2012, Vol. 482 Issue 7384, p221 

    Transcription factors and chromatin modifiers are important in the programming and reprogramming of cellular states during development. Transcription factors bind to enhancer elements and recruit coactivators and chromatin-modifying enzymes to facilitate transcription initiation. During...

  • Role of the Transcriptional Corepressor Bcor in Embryonic Stem Cell Differentiation and Early Embryonic Development. Wamstad, Joseph Alan; Corcoran, Connie Marie; Keating, Anne Marjorie; Bardwell, Vivian J. // PLoS ONE;2008, Vol. 3 Issue 7, p1 

    Bcor (BCL6 corepressor) is a widely expressed gene that is mutated in patients with X-linked Oculofaciocardiodental (OFCD) syndrome. BCOR regulates gene expression in association with a complex of proteins capable of epigenetic modification of chromatin. These include Polycomb group (PcG)...

  • Regulatory networks define phenotypic classes of human stem cell lines. Müller, Franz-Josef; Laurent, Louise C.; Kostka, Dennis; Ulitsky, Igor; Williams, Roy; Lu, Christina; Park, In-Hyun; Rao, Mahendra S.; Shamir, Ron; Schwartz, Philip H.; Schmidt, Nils O.; Loring, Jeanne F. // Nature;9/18/2008, Vol. 455 Issue 7211, p401 

    Stem cells are defined as self-renewing cell populations that can differentiate into multiple distinct cell types. However, hundreds of different human cell lines from embryonic, fetal and adult sources have been called stem cells, even though they range from pluripotent cells—typified by...

  • Nanog safeguards pluripotency and mediates germline development. Chambers, Ian; Silva, Jose; Colby, Douglas; Nichols, Jennifer; Nijmeijer, Bianca; Robertson, Morag; Vrana, Jan; Jones, Ken; Grotewold, Lars; Smith, Austin // Nature;12/14/2007, Vol. 450 Issue 7173, p1230 

    Nanog is a divergent homeodomain protein found in mammalian pluripotent cells and developing germ cells. Deletion of Nanog causes early embryonic lethality, whereas constitutive expression enables autonomous self-renewal of embryonic stem cells. Nanog is accordingly considered a core element of...

  • Inference of Gene Regulation via miRNAs During ES Cell Differentiation Using MiRaGE Method. Yoshizawa, Masato; Taguchi, Y-h.; Yasuda, Jun // International Journal of Molecular Sciences;Dec2011, Vol. 12 Issue 12, p9265 

    MicroRNA (miRNA) is a critical regulator of cell growth, differentiation, and development. To identify important miRNAs in a biological process, many bioinformatical tools have been developed. We have developed MiRaGE (MiRNA Ranking by Gene Expression) method to infer the regulation of gene...

  • Stem cells: Big roles for small RNAs. Slack, Frank J. // Nature;2/4/2010, Vol. 463 Issue 7281, p616 

    The article reports on the study which finds the role of microRNAs in the differentiation of the embryonic stem cells. It cites the function played by microRNA in regulating the gene expression, its discovery in the nematode Caenorhabditis elegans, and its crucial role in the biological...

  • Enrichment of cardiac differentiation by a large starting number of embryonic stem cells in embryoid bodies is mediated by the Wnt11-JNK pathway. Chen, Ming; Qian, Cheng; Bi, Lin-Lin; Zhao, Fang; Zhang, Guang-Yu; Wang, Zhi-Quan; Gan, Xue-Dong; Wang, Yang-Gan // Biotechnology Letters;Feb2015, Vol. 37 Issue 2, p475 

    Embryoid bodies (EBs) with large starting numbers of embryonic stem cells (ESCs) have a greater degree of cardiac differentiation than from low numbers of EBs. However, the biological roles of signaling molecules in these effects are not well understood. Here, we show that groups of EBs with...

  • Embryonic stem cells: the disagreement debate and embryonic stem cell research in Israel. Simonstein, F. // Journal of Medical Ethics;Oct2008, Vol. 34 Issue 10, p732 

    While some people claim that the present disagreement over embryonic stem (ES) cell research cannot be resolved, others argue that developing transparency and trust are key elements that could resolve the existing disagreements over such research. This paper reveals that transparency is not...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics