A non-canonical function of telomerase RNA in the regulation of developmental myelopoiesis in zebrafish : Nature Communications : Nature Publishing Group

A non-canonical function of telomerase RNA in the regulation of developmental myelopoiesis in zebrafish : Nature Communications : Nature Publishing Group

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

• Francisca Alcaraz-Pérez,
• Jesús García-Castillo,
• Diana García-Moreno,
• Azucena López-Muñoz,
• Monique Anchelin,
• Diego Angosto,
• Leonard I. Zon,
• Victoriano Mulero
• & María L. Cayuela

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Nature Communications

 

5,

 

Article number:

 

3228

 

doi:10.1038/ncomms4228

Received

 

17 October 2013 

Accepted

 

09 January 2014 

Published

 

05 February 2014

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Abstract

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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 TRdepletion is independent of telomere length and telomerase activity. Genetic analysis shows that TRmodulates 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.