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Endothelial Cells Are Essential for the Self-Renewal and Repopulation of Notch-Dependent Hematopoietic Stem Cells
Open accessAbstract
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.
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Wnt proteins are lipid-modified and can act as stem cell growth factors
Willert, K., Brown, J. D., Danenberg, E., Duncan, A. W., Weissman, I. L., Reya, T., Yates, J. R., & Nusse, R. (2003) · Nature · doi:10.1038/nature01611 · Cited by 2,257
Wolfe, M. S., Xia, W., Moore, C. L., Leatherwood, D. D., Ostaszewski, B., Rahmati, T., Donkor, I. O., & Selkoe, D. J. (1999) · Biochemistry · doi:10.1021/bi982562p · Cited by 289
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The bone marrow niche for haematopoietic stem cells
Morrison, S. J., & Scadden, D. T. (2014) · Nature · doi:10.1038/nature12984 · Cited by 2,451
The perivascular niche regulates breast tumour dormancy
Ghajar, C. M., Peinado, H., Mori, H., Matei, I. R., Evason, K. J., Brazier, H., Almeida, D., Koller, A., Hajjar, K. A., Stainier, D. Y. R., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2767 · Cited by 1,148
Adult haematopoietic stem cell niches
Crane, G. M., Jeffery, E., & Morrison, S. J. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.53 · Cited by 712
The brain tumor microenvironment
Charles, N. A., Holland, E. C., Gilbertson, R., Glass, R., & Kettenmann, H. (2011) · Glia · doi:10.1002/glia.21136 · Cited by 718
Frenette, P. S., Pinho, S., Lucas, D., & Scheiermann, C. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095919 · Cited by 462
Metadata
- Authors
- Butler, J. M., Nolan, D. J., Vertes, E. L., Varnum-Finney, B., Kobayashi, H., Hooper, A. T., Seandel, M., Shido, K., White, I. A., Kobayashi, M., Witte, L., May, C., Shawber, C., Kimura, Y., Kitajewski, J., Rosenwaks, Z., Bernstein, I. D., & Rafii, S.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 6
- Issue
- 3
- Pages
- 251-264
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2019524333
- Cited by
- 688
- References
- 2
- FWCI
- 31.96
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Butler, J. M., Nolan, D. J., Vertes, E. L., Varnum-Finney, B., Kobayashi, H., Hooper, A. T., Seandel, M., Shido, K., White, I. A., Kobayashi, M., Witte, L., May, C., Shawber, C., Kimura, Y., Kitajewski, J., Rosenwaks, Z., Bernstein, I. D., & Rafii, S. (2010). Endothelial Cells Are Essential for the Self-Renewal and Repopulation of Notch-Dependent Hematopoietic Stem Cells. Cell Stem Cell. https://doi.org/10.1016/j.stem.2010.02.001
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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