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Epigenetic profiles signify cell fate plasticity in unipotent spermatogonial stem and progenitor cells

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  • Ying Liu

    (Ansary Stem Cell Institute, Weill Cornell Medical College
    Chromatin Biology and Epigenetics, The Rockefeller University)

  • Eugenia G. Giannopoulou

    (New York City College of Technology, City University of New York
    Arthritis and Tissue Degeneration Program and the David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery)

  • Duancheng Wen

    (Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College)

  • Ilaria Falciatori

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge)

  • Olivier Elemento

    (HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College
    Weill Cornell Medical College)

  • C. David Allis

    (Chromatin Biology and Epigenetics, The Rockefeller University)

  • Shahin Rafii

    (Ansary Stem Cell Institute, Weill Cornell Medical College)

  • Marco Seandel

    (Weill Cornell Medical College)

Abstract

Spermatogonial stem and progenitor cells (SSCs) generate adult male gametes. During in vitro expansion, these unipotent murine cells spontaneously convert to multipotent adult spermatogonial-derived stem cells (MASCs). Here we investigate this conversion process through integrative transcriptomic and epigenomic analyses. We find in SSCs that promoters essential to maintenance and differentiation of embryonic stem cells (ESCs) are enriched with histone H3-lysine4 and -lysine 27 trimethylations. These bivalent modifications are maintained at most somatic promoters after conversion, bestowing MASCs an ESC-like promoter chromatin. At enhancers, the core pluripotency circuitry is activated partially in SSCs and completely in MASCs, concomitant with loss of germ cell-specific gene expression and initiation of embryonic-like programs. Furthermore, SSCs in vitro maintain the epigenomic characteristics of germ cells in vivo. Our observations suggest that SSCs encode innate plasticity through the epigenome and that both conversion of promoter chromatin states and activation of cell type-specific enhancers are prominent features of reprogramming.

Suggested Citation

  • Ying Liu & Eugenia G. Giannopoulou & Duancheng Wen & Ilaria Falciatori & Olivier Elemento & C. David Allis & Shahin Rafii & Marco Seandel, 2016. "Epigenetic profiles signify cell fate plasticity in unipotent spermatogonial stem and progenitor cells," Nature Communications, Nature, vol. 7(1), pages 1-13, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11275
    DOI: 10.1038/ncomms11275
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