Epigenetic Landscaping During hESC Differentiation to Neural Cells

Authors

  • Anna Golebiewska,

    1. Institute of Human Genetics, University of Newcastle Upon Tyne, International Centre for Life, United Kingdom
    2. North East Institute for Stem Cell Research, University of Newcastle Upon Tyne, International Centre for Life, United Kingdom
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  • Stuart P. Atkinson,

    1. Institute of Human Genetics, University of Newcastle Upon Tyne, International Centre for Life, United Kingdom
    2. North East Institute for Stem Cell Research, University of Newcastle Upon Tyne, International Centre for Life, United Kingdom
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  • Majlinda Lako,

    1. Institute of Human Genetics, University of Newcastle Upon Tyne, International Centre for Life, United Kingdom
    2. North East Institute for Stem Cell Research, University of Newcastle Upon Tyne, International Centre for Life, United Kingdom
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  • Lyle Armstrong

    Corresponding author
    1. Institute of Human Genetics, University of Newcastle Upon Tyne, International Centre for Life, United Kingdom
    2. North East Institute for Stem Cell Research, University of Newcastle Upon Tyne, International Centre for Life, United Kingdom
    • International Centre for Life, Central Parkway, Newcastle upon Tyne NE1 3BZ, U.K
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    • Telephone: 00-44-191-241-8695; Fax: 00-44-191-241-8666


  • Author contributions: A.G.: collection and assembly of data, manuscript writing; S.P.A.: collection and assembly of data, manuscript writing; M.L.: conception and design, manuscript writing; L.A.: conception and design, manuscript writing and financial support.

  • First published online in STEM CELLSExpress March 12, 2009

Abstract

The molecular mechanisms underlying pluripotency and lineage specification from embryonic stem cells (ESCs) are still largely unclear. To address the role of chromatin structure in maintenance of pluripotency in human ESCs (hESCs) and establishment of lineage commitment, we analyzed a panel of histone modifications at promoter sequences of genes involved in maintenance of pluripotency, self-renewal, and in early stages of differentiation. To understand the changes occurring at lineage-specific gene regulatory sequences, we have established an efficient purification system that permits the examination of two distinct populations of lineage committed cells; fluorescence activated cell sorted CD133+ CD45CD34 neural stem cells and β-III-tubulin+ putative neurons. Here we report the importance of other permissive marks supporting trimethylation of Lysine 4 H3 at the active stem cell promoters as well as poised bivalent and nonbivalent lineage-specific gene promoters in hESCs. Methylation of lysine 9 H3 was found to play a role in repression of pluripotency-associated and lineage-specific genes on differentiation. Moreover, presence of newly formed bivalent domains was observed at the neural progenitor stage. However, they differ significantly from the bivalent domains observed in hESCs, with a possible role of dimethylation of lysine 9 H3 in repressing the poised genes. STEM CELLS 2009;27:1298–1308

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