PUBLICATION

Hematopoietic stem cells develop in the absence of endothelial cadherin 5 expression

Authors
Anderson, H., Patch, T.C., Reddy, P.N., Hagedorn, E.J., Kim, P.G., Soltis, K.A., Chen, M.J., Tamplin, O.J., Frye, M., MacLean, G.A., Hübner, K., Bauer, D.E., Kanki, J.P., Vogin, G., Huston, N.C., Nguyen, M., Fujiwara, Y., Paw, B.H., Vestweber, D., Zon, L.I., Orkin, S.H., Daley, G.Q., Shah, D.I.
ID
ZDB-PUB-150920-6
Date
2015
Source
Blood   126(26): 2811-20 (Journal)
Registered Authors
Kanki, John, Nguyen, Minh Tu, Patch, Taylor, Paw, Barry, Shah, Dhvanit I., Tamplin, Owen, Zon, Leonard I.
Keywords
none
MeSH Terms
  • Animals
  • Antigens, CD/metabolism*
  • Cadherins/metabolism*
  • Cell Differentiation/physiology*
  • Cell Lineage/physiology
  • Electroporation
  • Embryo, Mammalian
  • Embryo, Nonmammalian
  • Flow Cytometry
  • Hemangioblasts/cytology*
  • Hematopoiesis/physiology*
  • Hematopoietic Stem Cells/cytology*
  • Immunohistochemistry
  • Mesonephros/embryology
  • Mice
  • Mice, Knockout
  • Microscopy, Confocal
  • Zebrafish
PubMed
26385351 Full text @ Blood
Abstract
Rare endothelial cells in the aorta-gonad-mesonephros (AGM) transition into hematopoietic stem cells (HSCs) during embryonic development. Lineage tracing experiments indicate that HSCs emerge from Cadherin 5 (Cdh5, VE-cadherin)(+) endothelial precursors, and isolated populations of Cdh5(+) cells from mouse embryos and embryonic stem (ES) cells can be differentiated into hematopoietic cells. Cdh5 has also been widely implicated as a marker of AGM-derived hemogenic endothelial cells. Since Cdh5(-/-) mice embryos die before the first HSCs emerge, it is unknown if Cdh5 has a direct role in HSC emergence. Our previous genetic screen yielded malbec (mlb(bw306)), a zebrafish mutant for cdh5, with normal embryonic and definitive blood. Utilizing time-lapse confocal imaging, parabiotic surgical pairing of zebrafish embryos, and blastula transplantation assays, we show that HSCs emerge, migrate, engraft, and differentiate in the absence of cdh5 expression. By tracing Cdh5(-/-)GFP(+/+) cells in chimeric mice, we demonstrated that Cdh5(-/-) GFP(+/+) HSCs emerging from E10.5 and E11.5 AGM or derived from E13.5 fetal liver not only differentiate into hematopoietic colonies but also engraft and reconstitute multi-lineage adult blood. We also developed a conditional mouse Cdh5 knockout (Cdh5(flox/flox):Scl-Cre-ER(T)) and demonstrated that multipotent hematopoietic colonies form despite the absence of Cdh5. These data establish that Cdh5, a marker of hemogenic endothelium in the AGM, is dispensable for the transition of hemogenic endothelium to HSCs.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping