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Normal Hemopoiesis

Zebrafish microRNA-126 determines hematopoietic cell fate through c-Myb

Leukemia volume 25, pages 506–514 (2011)Cite this article

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Abstract

Precise regulatory mechanisms are required to appropriately modulate the cellular levels of transcription factors controlling cell fate decisions during blood cell development. In this study, we show that miR-126 is a novel physiological regulator of the proto-oncogene c-myb during definitive hematopoiesis. We show that knockdown of miR-126 results in increased c-Myb levels and promotes erythropoiesis at the expense of thrombopoiesis in vivo. We further provide evidence that specification of thrombocyte versus erythrocyte cell lineages is altered by the concerted activities of the microRNAs (miRNAs) miR-126 and miR-150. Both miRNAs are required but not sufficient individually to precisely regulate the cell fate decision between erythroid and megakaryocytic lineages during definitive hematopoiesis in vivo. These results support the notion that miRNAs not only function to provide precision to developmental programs but also are essential determinants in the control of variable potential functions of a single gene during hematopoiesis.

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Acknowledgements

We thank R Hoffmans, U Pyati and N Bushati for critical comments on the manuscript and L Zon for the Tg(c-myb:EGFP) zebrafish line. This work was supported by the NIH grant CA93152 (ATL). EMP is the recipient of a Clinical Research Training Fellowship from Leukemia and Lymphoma Research UK. NB is a Special Fellow of the Leukemia and Lymphoma Society.

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  1. C Grabher and E M Payne: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    C Grabher, E M Payne, A B Johnston, N Bolli, J P Kanki & A T Look

  2. Institute of Cancer, Center for Medical Oncology, Barts and the London School of Medicine, London, UK

    E M Payne

  3. Division of Stem Cell and Developmental Biology, Campbell Family Institute for Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada

    E Lechman & J E Dick

  4. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada

    E Lechman & J E Dick

  5. Division of Hematology/Oncology, Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, MA, USA

    A T Look

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Correspondence to C Grabher.

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Grabher, C., Payne, E., Johnston, A. et al. Zebrafish microRNA-126 determines hematopoietic cell fate through c-Myb. Leukemia 25, 506–514 (2011). https://doi.org/10.1038/leu.2010.280

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