PUBLICATION

Hematopoietic stem cell development is dependent on blood flow

Authors
North, T.E., Goessling, W., Peeters, M., Li, P., Ceol, C., Lord, A.M., Weber, G.J., Harris, J., Cutting, C.C., Huang, P., Dzierzak, E., and Zon, L.I.
ID
ZDB-PUB-090526-18
Date
2009
Source
Cell   137(4): 736-748 (Journal)
Registered Authors
Ceol, Craig, Goessling, Wolfram, Lord, Allegra, North, Trista, Weber, Gerhard, Zon, Leonard I.
Keywords
DEVBIO, STEMCELL
MeSH Terms
  • Embryo, Nonmammalian/metabolism
  • Blood Physiological Phenomena*
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase Type III/metabolism
  • Mice
  • Nitric Oxide/metabolism
  • Animals
  • Hematopoietic Stem Cells/cytology*
  • Hematopoiesis*
  • Zebrafish
  • Embryo, Mammalian/metabolism
(all 11)
PubMed
19450519 Full text @ Cell
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.
Genes / Markers
Figures
Figure Gallery (18 images) / 2
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WT + MO1-nos1standard conditionsPrim-25
WT + MO1-nos2astandard conditionsPrim-25
WT + MO2-nos1standard conditionsPrim-25
WT + MO2-nos2astandard conditionsPrim-25
tnnt2aunspecified/unspecifiedstandard conditionsPrim-25
tnnt2aunspecified/unspecifiedstandard conditionsPrim-25
tnnt2aunspecified/unspecifiedstandard conditionsPrim-25
tnnt2aunspecified/unspecifiedstandard conditionsPrim-25
1 - 8 of 8
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ta52b
    		Point Mutation
    tnnt2a_unspecified
      		Unspecified
      w32TgTransgenic Insertion
        w34TgTransgenic Insertion
          y1TgTransgenic Insertion
            zf73TgTransgenic Insertion
              zf169TgTransgenic Insertion
                1 - 7 of 7
                Show
                Human Disease / Model
                No data available
                Sequence Targeting Reagents
                Target Reagent Reagent Type
                nos1MO1-nos1MRPHLNO
                nos1MO2-nos1MRPHLNO
                nos2aMO1-nos2aMRPHLNO
                nos2aMO2-nos2aMRPHLNO
                1 - 4 of 4
                Show
                Fish
                Fish
                mib1ta52b/ta52b
                tnnt2aunspecified/unspecified
                w32Tg
                w34Tg
                WT
                WT + MO1-nos1
                WT + MO1-nos2a
                WT + MO2-nos1
                WT + MO2-nos2a
                y1Tg/y1Tg
                1 - 10 of 13
                Show
                Antibodies
                No data available
                Orthology
                No data available
                Engineered Foreign Genes
                Marker Marker Type Name
                DsRedEFGDsRed
                EGFPEFGEGFP
                GFPEFGGFP
                1 - 3 of 3
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                Mapping
                No data available
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                Citation
                North, T.E., Goessling, W., Peeters, M., Li, P., Ceol, C., Lord, A.M., Weber, G.J., Harris, J., Cutting, C.C., Huang, P., Dzierzak, E., and Zon, L.I. (2009) Hematopoietic stem cell development is dependent on blood flow. Cell. 137(4):736-748.