Tel/Etv6 is an essential and selective regulator of adult hematopoietic stem cell survival

  1. Hanno Hock1,2,
  2. Eliza Meade1,
  3. Sarah Medeiros1,
  4. Jeffrey W. Schindler1,
  5. Peter J.M. Valk1,
  6. Yuko Fujiwara1,4, and
  7. Stuart H. Orkin1,3,4,5
  1. 1Division of Hematology/Oncology, Children's Hospital, 2Department of Medical Oncology, and 3Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA; 4Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA

Abstract

Hematopoietic stem cells (HSCs) sustain blood formation throughout life. Pathways regulating maintenance of adult HSCs are largely unknown. Here we report that the Ets-related transcription factor Tel/Etv6, the product of a locus frequently involved in translocations in leukemia, is a selective regulator of HSC survival. Following inactivation of Tel/Etv6, HSCs are lost in the adult bone marrow but their progeny are unaffected and transiently sustain blood formation. Accordingly, absence of Tel/Etv6 after lineage commitment is ostensibly without consequence except for unexpected impairment of maturation of megakaryocytes. Thus, we establish Tel/Etv6 as a selective and essential regulator of postembryonic HSCs.

Keywords

Footnotes

  • Supplemental material is available at http://www.genesdev.org.

  • Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1239604.

  • ↵5 Corresponding author. E-MAIL stuart_orkin{at}dfci.harvard.edu; FAX (617) 730 0222.

    • Accepted August 4, 2004.
    • Received July 14, 2004.
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  1. Published in Advance September 15, 2004, doi: 10.1101/gad.1239604 Genes & Dev. 2004. 18: 2336-2341 Copyright © 2004, by Cold Spring Harbor Laboratory Press

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