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Endoglin is not critical for hematopoietic stem cell engraftment and reconstitution but regulates adult erythroid development

In English

Författare

Summary, in English

Endoglin is a transforming growth factor-beta (TGF-beta) accessory receptor recently identified as being highly expressed on long-term repopulating hematopoietic stem cells (HSC) However, little is known regarding its function in these cells. We have used two complementary approaches toward understanding endoglin's role in HSC biology: one that efficiently knocks down expression via lentiviral-driven short hairpin RNA and another that uses retroviral-mediated overexpression. Altering endoglin expression had functional consequences for hematopoietic progenitors in vitro such that endoglin-suppressed myeloid progenitors (colony-forming unit-granulocyte macrophage) displayed a higher degree of sensitivity to TGF-beta-mediated growth inhibition, whereas endoglin-overexpressing cells were partially resistant. However, transplantation of transduced bone marrow enriched in primitive hematopoietic stem and progenitor cells revealed that neither endoglin suppression nor endoglin overexpression affected the ability of stem cells to short-term or long-term repopulate recipient marrow. Furthermore, transplantation of cells altered in endoglin expression yielded normal white blood cell proportions and peripheral blood platelets. Interestingly, decreasing endoglin expression increased the clonogenic capacity of early blast-forming unit-erythroid progenitors, whereas overexpression compromised erythroid differentiation at the basophilic erythroblast phase, suggesting a pivotal role for endoglin at key stages of adult erythropoietic development.

Publiceringsår

2007

Språk

Engelska

Sidor

2809-2819

Publikation/Tidskrift/Serie

Stem Cells

Volym

25

Issue

11

Dokumenttyp

Artikel i tidskrift

Förlag

AlphaMed Press

Ämne

  • Cell and Molecular Biology

Nyckelord

  • erythropoiesis
  • RNA interference
  • hematopoiesis
  • stem cells

Status

Published

Forskningsgrupp

  • Immunology
  • Stem cell and red cell biology

ISBN/ISSN/Övrigt

  • ISSN: 1549-4918