title: Mouse extraembryonic arterial vessels harbor precursors capable of maturing into definitive HSCs.
abstract: During mouse development, definitive hematopoietic stem cells (dHSCs) emerge by late E10.5 to E11 in several hematopoietic sites. Of them, the aorta-gonad-mesonephros (AGM) region drew particular attention owing to its capacity to autonomously initiate and expand dHSCs in culture, indicating its key role in HSC development. The dorsal aorta contains characteristic hematopoietic clusters and is the initial site of dHSC emergence, where they mature through vascular endothelial (VE)-cadherin(+)CD45(-)CD41(low) (type 1 pre-HSCs) and VE-cadherin(+)CD45(+) (type 2 pre-HSCs) intermediates. Although dHSCs were also found in other embryonic niches (placenta, yolk sac, and extraembryonic vessels), attempts to detect their HSC initiating potential have been unsuccessful to date. Extraembryonic arterial vessels contain hematopoietic clusters, suggesting that they develop HSCs, but functional evidence for this has been lacking. Here we show that umbilical cord and vitelline arteries (VAs), but not veins, contain pre-HSCs capable of maturing into dHSCs in the presence of exogenous interleukin 3, although in fewer numbers than the AGM region, and that pre-HSC activity in VAs increases with proximity to the embryo proper. Our functional data strongly suggest that extraembryonic arteries can actively contribute to adult hematopoiesis.
authors.affiliation: Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, Scotland, United Kingdom; and.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Gordon-Keylock
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Sobiesiak
authors.forename: Stanislav
authors.initials: S
authors.lastname: Rybtsov
authors.forename: Kate
authors.initials: K
authors.lastname: Moore
authors.forename: Alexander
authors.initials: A
authors.lastname: Medvinsky
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014469:Umbilical Arteries / Q000166:cytology* / Q000196:embryology; D014816:Vitelline Duct / Q000098:blood supply / Q000166:cytology* / Q000196:embryology