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Embryonic stem cell potency fluctuates with endogenous retrovirus activity.

Nature | Jul 5, 2012

Embryonic stem (ES) cells are derived from blastocyst-stage embryos and are thought to be functionally equivalent to the inner cell mass, which lacks the ability to produce all extraembryonic tissues. Here we identify a rare transient cell population within mouse ES and induced pluripotent stem (iPS) cell cultures that expresses high levels of transcripts found in two-cell (2C) embryos in which the blastomeres are totipotent. We genetically tagged these 2C-like ES cells and show that they lack the inner cell mass pluripotency proteins Oct4 (also known as Pou5f1), Sox2 and Nanog, and have acquired the ability to contribute to both embryonic and extraembryonic tissues. We show that nearly all ES cells cycle in and out of this privileged state, which is partially controlled by histone-modifying enzymes. Transcriptome sequencing and bioinformatic analyses showed that many 2C transcripts are initiated from long terminal repeats derived from endogenous retroviruses, suggesting this foreign sequence has helped to drive cell-fate regulation in placental mammals.

Pubmed ID: 22722858 RIS Download

Mesh terms: Animals | Cell Dedifferentiation | Cell Lineage | Chimera | Chromatin | Embryo, Mammalian | Embryonic Stem Cells | Endogenous Retroviruses | Epigenesis, Genetic | Female | Gene Expression Regulation, Developmental | Genes, Reporter | Histones | Induced Pluripotent Stem Cells | Lysine | Methylation | Mice | Phenotype | Pluripotent Stem Cells | Terminal Repeat Sequences | Totipotent Stem Cells | Transcriptome

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Associated grants

  • Agency: European Research Council, Id: 268721
  • Agency: NINDS NIH HHS, Id: R37 NS037116
  • Agency: NINDS NIH HHS, Id: R37NS037116
  • Agency: Howard Hughes Medical Institute, Id:

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Database for Annotation Visualization and Integrated Discovery

A database which provides a comprehensive set of functional annotation tools for investigators to understand biological meaning behind large list of genes. For any given gene list, DAVID tools are able to perform a variety of actions such as identifying enriched biological themes (particularly GO terms), discovering enriched functional-related gene groups, clustering redundant annotation terms, and visualizing genes on BioCarta and KEGG pathway maps.


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Genetic Information Research Institute

GIRI is a private, non-profit research institution founded in 1994. Our mission is to understand biological processes which alter the genetic makeup of different organisms, as a basis for potential gene therapy and genome engineering techniques. We pursue and promote original peer-reviewed, public domain research on genetic information (DNA sequence data), as well as dissemination of databases and computer software related to this research. Our research is heavily based on computer power and human skills different from those applied in classical molecular biology and genetics.


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An integrated biological knowledgebase and comprehensive set of functional annotation tools for investigators to understand biological meaning behind large lists of genes. For any given gene list, DAVID tools are able to: - Identify enriched biological themes, particularly GO terms - Discover enriched functional-related gene groups - Cluster redundant annotation terms - Visualize genes on BioCarta & KEGG pathway maps - Display related many-genes-to-many-terms on 2-D view. - Search for other functionally related genes not in the list - List interacting proteins - Explore gene names in batch - Link gene-disease associations - Highlight protein functional domains and motifs - Redirect to related literatures - Convert gene identifiers from one type to another.


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