Engraftment and reconstitution of hematopoiesis is dependent on VEGFR2-mediated regeneration of sinusoidal endothelial cells. Academic Article uri icon

Overview

MeSH

  • Animals
  • Ataxin-1
  • Ataxins
  • Blood Vessels
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Sequence Deletion
  • Signal Transduction
  • Whole-Body Irradiation

MeSH Major

  • Bone Marrow
  • Endothelium, Vascular
  • Hematopoiesis
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells
  • Regeneration
  • Vascular Endothelial Growth Factor Receptor-2

abstract

  • Myelosuppression damages the bone marrow (BM) vascular niche, but it is unclear how regeneration of bone marrow vessels contributes to engraftment of transplanted hematopoietic stem and progenitor cells (HSPCs) and restoration of hematopoiesis. We found that chemotherapy and sublethal irradiation induced minor regression of BM sinusoidal endothelial cells (SECs), while lethal irradiation induced severe regression of SECs and required BM transplantation (BMT) for regeneration. Within the BM, VEGFR2 expression specifically demarcated a continuous network of arterioles and SECs, with arterioles uniquely expressing Sca1 and SECs uniquely expressing VEGFR3. Conditional deletion of VEGFR2 in adult mice blocked regeneration of SECs in sublethally irradiated animals and prevented hematopoietic reconstitution. Similarly, inhibition of VEGFR2 signaling in lethally irradiated wild-type mice rescued with BMT severely impaired SEC reconstruction and prevented engraftment and reconstitution of HSPCs. Therefore, regeneration of SECs via VEGFR2 signaling is essential for engraftment of HSPCs and restoration of hematopoiesis.

publication date

  • March 6, 2009

has subject area

  • Animals
  • Ataxin-1
  • Ataxins
  • Blood Vessels
  • Bone Marrow
  • Endothelium, Vascular
  • Hematopoiesis
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Regeneration
  • Sequence Deletion
  • Signal Transduction
  • Vascular Endothelial Growth Factor Receptor-2
  • Whole-Body Irradiation

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3228275

Digital Object Identifier (DOI)

  • 10.1016/j.stem.2009.01.006

PubMed ID

  • 19265665

Additional Document Info

start page

  • 263

end page

  • 274

volume

  • 4

number

  • 3