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A non-canonical function of telomerase RNA in the regulation of developmental myelopoiesis in zebrafish

Author

Listed:
  • Francisca Alcaraz-Pérez

    (Telomerase, Aging and Cancer Group, Research Unit, CIBERehd, University Hospital ‘Virgen de la Arrixaca’
    Instituto Murciano de Investigación Biosanitaria (IMIB))

  • Jesús García-Castillo

    (Telomerase, Aging and Cancer Group, Research Unit, CIBERehd, University Hospital ‘Virgen de la Arrixaca’
    Instituto Murciano de Investigación Biosanitaria (IMIB))

  • Diana García-Moreno

    (Telomerase, Aging and Cancer Group, Research Unit, CIBERehd, University Hospital ‘Virgen de la Arrixaca’
    Instituto Murciano de Investigación Biosanitaria (IMIB)
    Facultad de Biología, Universidad de Murcia)

  • Azucena López-Muñoz

    (Instituto Murciano de Investigación Biosanitaria (IMIB)
    Facultad de Biología, Universidad de Murcia)

  • Monique Anchelin

    (Telomerase, Aging and Cancer Group, Research Unit, CIBERehd, University Hospital ‘Virgen de la Arrixaca’
    Instituto Murciano de Investigación Biosanitaria (IMIB))

  • Diego Angosto

    (Instituto Murciano de Investigación Biosanitaria (IMIB)
    Facultad de Biología, Universidad de Murcia)

  • Leonard I. Zon

    (Howard Hughes Medical Institute
    Stem Cell Program, Children’s Hospital Boston
    Children’s Hospital Boston, Harvard Stem Cell Institute, Harvard Medical School)

  • Victoriano Mulero

    (Instituto Murciano de Investigación Biosanitaria (IMIB)
    Facultad de Biología, Universidad de Murcia)

  • María L. Cayuela

    (Telomerase, Aging and Cancer Group, Research Unit, CIBERehd, University Hospital ‘Virgen de la Arrixaca’
    Instituto Murciano de Investigación Biosanitaria (IMIB))

Abstract

Dyskeratosis congenita (DC) is an inherited disorder with mutations affecting telomerase or telomeric proteins. DC patients usually die of bone marrow failure. Here we show that genetic depletion of the telomerase RNA component (TR) in the zebrafish results in impaired myelopoiesis, despite normal development of haematopoietic stem cells (HSCs). The neutropenia caused by TR depletion is independent of telomere length and telomerase activity. Genetic analysis shows that TR modulates the myeloid–erythroid fate decision by controlling the levels of the master myeloid and erythroid transcription factors spi1 and gata1, respectively. The alteration in spi1 and gata1 levels occurs through stimulation of gcsf and mcsf. Our model of TR deficiency in the zebrafish illuminates the non-canonical roles of TR, and could establish therapeutic targets for DC.

Suggested Citation

  • Francisca Alcaraz-Pérez & Jesús García-Castillo & Diana García-Moreno & Azucena López-Muñoz & Monique Anchelin & Diego Angosto & Leonard I. Zon & Victoriano Mulero & María L. Cayuela, 2014. "A non-canonical function of telomerase RNA in the regulation of developmental myelopoiesis in zebrafish," Nature Communications, Nature, vol. 5(1), pages 1-11, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4228
    DOI: 10.1038/ncomms4228
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