Send to

Choose Destination
See comment in PubMed Commons below
Circulation. 2008 Jul 8;118(2):157-65. doi: 10.1161/CIRCULATIONAHA.107.754978.

Specific Jagged-1 signal from bone marrow microenvironment is required for endothelial progenitor cell development for neovascularization.

Author information

  • 1Stem Cell Translational Research Laboratory, RIKEN Center For Developmental Biology/Institute of Biomedical Research and Innovation, Kobe, Japan.



Despite accumulating evidence that proves the pivotal role of endothelial progenitor cells (EPCs) in ischemic neovascularization, the key signaling cascade that regulates functional EPC kinetics remains unclear.


In this report, we show that inactivation of specific Jagged-1 (Jag-1)-mediated Notch signals leads to inhibition of postnatal vasculogenesis in hindlimb ischemia via impairment of proliferation, survival, differentiation, and mobilization of bone marrow-derived EPCs. Bone marrow-derived EPCs obtained from Jag-1-/- mice, but not Delta-like (Dll)-1-/- mice, demonstrated less therapeutic potential for ischemic neovascularization than EPCs from the wild type. In contrast, a gain-of-function study using 3T3 stromal cells overexpressing Notch ligand revealed that Jag-1-mediated Notch signals promoted EPC commitment, which resulted in enhanced neovascularization. The impaired neovascularization in Jag-1-/- mice was profoundly rescued by transplantation of Jag-1-stimulated EPCs.


These data indicate that specific Jag-1-derived Notch signals from the bone marrow microenvironment are critical for EPC-mediated vasculogenesis, thus providing an important clue for modulation of strategies for therapeutic neovascularization.

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center