Endothelial Jagged-1 Is necessary for homeostatic and regenerative hematopoiesis

Michael G. Poulos, Peipei Guo, Natalie M. Kofler, Sandra Pinho, Michael C. Gutkin, Anastasia Tikhonova, Iannis Aifantis, Paul S. Frenette, Jan Kitajewski, Shahin Rafii, Jason M. Butler

Research output: Contribution to journalArticle

121 Scopus citations

Abstract

The bone marrow (BM) microenvironment is composed of multiple niche cells that, by producing paracrine factors, maintain and regenerate the hematopoietic stem cell (HSC) pool (Morrison and Spradling, 2008). We have previously demonstrated that endothelial cells support the proper regeneration of the hematopoietic system following myeloablation (Butler etal., 2010; Hooper etal., 2009; Kobayashi etal., 2010). Here, we demonstrate that expression of the angiocrine factor Jagged-1, supplied by the BM vascular niche, regulates homeostatic and regenerative hematopoiesis through a Notch-dependent mechanism. Conditional deletion of Jagged-1 in endothelial cells (Jag1(ECKO) mice) results in a profound decrease in hematopoiesis and premature exhaustion of the adult HSC pool, whereas quantification and functional assays demonstrate that loss of Jagged-1 does not perturb vascular or mesenchymal compartments. Taken together, these data demonstrate that the instructive function of endothelial-specific Jagged-1 is required to support the self-renewal and regenerative capacity of HSCs in the adult BM vascular niche

Original languageEnglish (US)
Pages (from-to)1022-1034
Number of pages13
JournalCell Reports
Volume4
Issue number5
DOIs
StatePublished - May 12 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Poulos, M. G., Guo, P., Kofler, N. M., Pinho, S., Gutkin, M. C., Tikhonova, A., Aifantis, I., Frenette, P. S., Kitajewski, J., Rafii, S., & Butler, J. M. (2013). Endothelial Jagged-1 Is necessary for homeostatic and regenerative hematopoiesis. Cell Reports, 4(5), 1022-1034. https://doi.org/10.1016/j.celrep.2013.07.048