Hematopoietic Stem Cell Development Is Dependent on Blood Flow

Trista E. North, Wolfram Goessling, Marian Peeters, Pulin Li, Craig Ceol, Allegra M. Lord, Gerhard J. Weber, James Harris, Claire C. Cutting, Paul Huang, Elaine Dzierzak, Leonard I. Zon

Research output: Contribution to journalArticlepeer-review

Abstract

During vertebrate embryogenesis, hematopoietic stem cells (HSCs) arise in the aorta-gonads-mesonephros (AGM) region. We report here that blood flow is a conserved regulator of HSC formation. In zebrafish, chemical blood flow modulators regulated HSC development, and silent heart (sih) embryos, lacking a heartbeat and blood circulation, exhibited severely reduced HSCs. Flow-modifying compounds primarily affected HSC induction after the onset of heartbeat; however, nitric oxide (NO) donors regulated HSC number even when treatment occurred before the initiation of circulation, and rescued HSCs in sih mutants. Morpholino knockdown of nos1 (nnos/enos) blocked HSC development, and its requirement was shown to be cell autonomous. In the mouse, Nos3 (eNos) was expressed in HSCs in the AGM. Intrauterine Nos inhibition or embryonic Nos3 deficiency resulted in a reduction of hematopoietic clusters and transplantable murine HSCs. This work links blood flow to AGM hematopoiesis and identifies NO as a conserved downstream regulator of HSC development.
Original languageEnglish
Pages (from-to)736-748
JournalCell
Volume137
Issue number4
DOIs
Publication statusPublished - May 2009

Keywords

  • DEVBIO
  • STEMCELL

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