Alcaraz-Pérez F, García-Castillo J, García-Moreno D, López-Muñoz A, Anchelin M, Angosto D, Zon LI, Mulero V, Cayuela ML. A non-canonical function of telomerase RNA in the regulation of developmental myelopoiesis in zebrafish. Nat Commun. 2014; 5:3228.

Citation

Alcaraz-Pérez F, García-Castillo J, García-Moreno D, López-Muñoz A, Anchelin M, Angosto D, Zon LI, Mulero V, Cayuela ML. 2014. A non-canonical function of telomerase RNA in the regulation of developmental myelopoiesis in zebrafish. Nature communications. 5:3228. Pubmed: 24496182 DOI:10.1038/ncomms4228

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.

Related Faculty

Leonard Zon, M.D.

Zon Lab

The Zon laboratory aims to dissect how assaults to the hematopoietic system cause severe diseases such as leukemias, lymphomas, and anemias. They investigate hematopoietic development and disease using chemical screens, genetic screens, and analysis of novel transgenic lines in zebrafish.