Hematopoietic stem cells contribute to lymphatic endothelium

Shuguang Jiang, Alexis S. Bailey, Devorah Goldman, John R. Swain, Melissa Wong, Philip Streeter, William Fleming

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Background: Although the lymphatic system arises as an extension of venous vessels in the embryo, little is known about the role of circulating progenitors in the maintenance or development of lymphatic endothelium. Here, we investigated whether hematopoietic stem cells (HSCs) have the potential to give rise to lymphatic endothelial cells (LEC). Methodology/Principal Findings: Following the transfer of marked HSCs into irradiated recipients, donor-derived LEC that co-express the lymphatic endothelial markers Lyve-1 and VEGFR-3 were identified in several tissues. HSC-derived LEC persisted for more than 12 months and contributed to, ∼3-4% of lymphatic vessels. Donor-derived LECs were not detected in mice transplanted with common myeloid progenitors and granulocyte/macrophage progenitors, suggesting that myeloid lineage commitment is not a requisite step in HSC contribution to lymphatic endothelium. Analysis of parabiotic mice revealed direct evidence for the existence of functional, circulating lymphatic progenitors in the absence of acute injury. Furthermore, the transplantation of HSCs into ApcMin/+ mice resulted in the incorporation of donor-derived LEC into the lymphatic vessels of spontaneously arising intestinal tumors. Conclusions/Significance: Our results indicate that HSCs can contribute to normal and tumor associated lymphatic endothelium. These findings suggest that the modification of HSCs may be a novel approach for targeting tumor metastasis and attenuating diseases of the lymphatic system.

Original languageEnglish (US)
Article numbere3812
JournalPLoS One
Volume3
Issue number11
DOIs
StatePublished - Nov 26 2008

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Lymphatic Endothelium
Hematopoietic Stem Cells
endothelium
Stem cells
Endothelial cells
endothelial cells
Endothelial Cells
Lymphatic System
Lymphatic Vessels
Tumors
neoplasms
Vascular Endothelial Growth Factor Receptor-3
mice
vascular endothelial growth factor receptor-3
Myeloid Progenitor Cells
Neoplasms
Granulocyte-Macrophage Progenitor Cells
lymphatic system
Hematopoietic Stem Cell Transplantation
lymphatic diseases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Hematopoietic stem cells contribute to lymphatic endothelium. / Jiang, Shuguang; Bailey, Alexis S.; Goldman, Devorah; Swain, John R.; Wong, Melissa; Streeter, Philip; Fleming, William.

In: PLoS One, Vol. 3, No. 11, e3812, 26.11.2008.

Research output: Contribution to journalArticle

Jiang, Shuguang ; Bailey, Alexis S. ; Goldman, Devorah ; Swain, John R. ; Wong, Melissa ; Streeter, Philip ; Fleming, William. / Hematopoietic stem cells contribute to lymphatic endothelium. In: PLoS One. 2008 ; Vol. 3, No. 11.
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