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XB-ART-48503
Dev Cell April 20, 2010; 18 (4): 569-78.

Tel1/ETV6 specifies blood stem cells through the agency of VEGF signaling.



Abstract
The regulation of stem cell ontogeny is poorly understood. We show that the leukemia-associated Ets transcription factor, Tel1/ETV6, specifies the first hematopoietic stem cells (HSCs) in the dorsal aorta (DA). In contrast, Tel1/ETV6 has little effect on embryonic blood formation, further distinguishing the programming of the long- and short-term blood populations. Consistent with the notion of concordance of arterial and HSC programs, we show that Tel1/ETV6 is also required for the specification of the DA as an artery. We further show that Tel1/ETV6 acts by regulating the transcription of VegfA in both the lateral plate mesoderm and also in the somites. Exogenous VEGFA rescues Tel1/ETV6 morphants, and depletion of VEGFA or its receptor, Flk1, largely phenocopies Tel1/ETV6 depletion. Few such links between intrinsic and extrinsic programming of stem cells have been reported previously. Our data place Tel1/ETV6 at the apex of the genetic regulatory cascade leading to HSC production.

PubMed ID: 20412772
Article link: Dev Cell
Grant support: [+]
Genes referenced: atm dll4 efnb2 etv6 flt1 flt4 gata2 gfi1 kcnh2 kdr lmo2 notch1 notch4 notch4.2 odc1 runx1 spib tal1 tek vegfa
Morpholinos: etv6 MO1 etv6 MO2 kdr MO1 vegfa MO2


Article Images: [+] show captions


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