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TRF1 is a stem cell marker and is essential for the generation of induced pluripotent stem cells

Author

Listed:
  • Ralph P. Schneider

    (Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO))

  • Ianire Garrobo

    (Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO))

  • Miguel Foronda

    (Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO))

  • Jose A. Palacios

    (Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO))

  • Rosa M. Marión

    (Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO))

  • Ignacio Flores

    (Regeneration and Aging group, Cardiovascular Development and Repair Program, Spanish National Center for Cardiovascular Research (CNIC))

  • Sagrario Ortega

    (Transgenics Unit, Biotechnololy Program, Spanish National Cancer Research Centre (CNIO))

  • Maria A. Blasco

    (Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO))

Abstract

TRF1 is a component of the shelterin complex that protects chromosome ends. TRF1 deficiency leads to early embryonic lethality and to severe organ atrophy when deleted in adult tissues. Here we generate a reporter mouse carrying a knock-in eGFP-TRF1 fusion allele to study the role of TRF1 in stem cell biology and tissue homeostasis. We find that eGFP–TRF1 expression in mice is maximal in known adult stem cell compartments and show that TRF1 ensures their functionality. eGFP–TRF1 is highly expressed in induced pluripotent stem cells, uncoupled from the telomere elongation associated with reprogramming. Selection of eGFP–TRF1-high induced pluripotent stem cells correlates with higher pluripotency as indicated by their ability to form teratomas and chimeras. We further show that TRF1 is necessary for both induction and maintenance of pluripotency, and that TRF1 is a direct transcriptional target of Oct3/4.

Suggested Citation

  • Ralph P. Schneider & Ianire Garrobo & Miguel Foronda & Jose A. Palacios & Rosa M. Marión & Ignacio Flores & Sagrario Ortega & Maria A. Blasco, 2013. "TRF1 is a stem cell marker and is essential for the generation of induced pluripotent stem cells," Nature Communications, Nature, vol. 4(1), pages 1-16, October.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2946
    DOI: 10.1038/ncomms2946
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