Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells
By J. Butler, D. Nolan, Eva L.Vertes, B. Varnum‐Finney, Hideki Kobayashi, A. Hooper, M. Seandel, K. Shido, Ian A. White, Mariko Kobayashi and 8 more. Cell Stem Cell, 2010
671 citations recorded by the source corpus.
Bone marrow endothelial cells (ECs) are essential for reconstitution of hematopoiesis, but their role in self-renewal of long term-hematopoietic stem cells (LT-HSCs) is unknown. We have developed angiogenic models to demonstrate that EC-derived angiocrine growth factors support in vitro self-renewal and in vivo repopulation of authentic LT-HSCs. In serum/cytokine-free co-cultures, ECs through direct cellular contact, stimulated incremental expansion of repopulating CD34−Flt3−cKit+Lineage−Sca1+ LT-HSCs, which retained their self-renewal ability, as determined by single cell and serial transplantation assays. Angiocrine expression of Notch-ligands by ECs promoted proliferation and prevented exhaustion of LT-HSCs derived from wild-type, but not Notch1/Notch2 deficient mice. In transgenic notch-reporter (TNR.Gfp) mice, regenerating TNR.Gfp+ LT-HSCs were detected in cellular contact with sinusoidal ECs and interfering with angiocrine, but not perfusion function, of SECs impaired repopulation of TNR.Gfp+ LT-HSCs. ECs establish an instructive vascular niche for clinical scale expansion of LT-HSCs and a cellular platform to identify stem cell-active trophogens.
Subfields: Cell Biology, Hematology
View Paper: https://www.semanticscholar.org/paper/cf4784da7ff61af7cf6b1eff4942eeeb45638867
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Citations in the corpus
- The brain tumor microenvironment (2011, background): “Notch signaling from endothelial cells to hematopoetic stem cells (HSC) via expression of notch ligands has been shown to drive the self-renewal characteristics and in vivo repopulation of long-term HSCs that lie adjacent to the vasculature (Butler et al., 2010).”