Endothelial Jagged-1 is necessary for homeostatic and regenerative hematopoiesis. Academic Article uri icon

Overview

MeSH

  • Animals
  • Homeostasis
  • Jagged-1 Protein
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Serrate-Jagged Proteins
  • Signal Transduction

MeSH Major

  • Calcium-Binding Proteins
  • Endothelial Cells
  • Hematopoiesis
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins

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 et al., 2010; Hooper et al., 2009; Kobayashi et al., 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. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

publication date

  • September 12, 2013

has subject area

  • Animals
  • Calcium-Binding Proteins
  • Endothelial Cells
  • Hematopoiesis
  • Homeostasis
  • Intercellular Signaling Peptides and Proteins
  • Jagged-1 Protein
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Serrate-Jagged Proteins
  • Signal Transduction

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3805263

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2013.07.048

PubMed ID

  • 24012753

Additional Document Info

start page

  • 1022

end page

  • 1034

volume

  • 4

number

  • 5