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

Moody, Jennifer LU ; Singbrant, Sofie LU ; Karlsson, Göran LU ; Blank Savukinas, Ulrika LU ; Aspling, Marie LU ; Flygare, Johan LU ; Bryder, David LU and Karlsson, Stefan LU (2007) In Stem Cells 25(11). p.2809-2819
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
erythropoiesis, RNA interference, hematopoiesis, stem cells
in
Stem Cells
volume
25
issue
11
pages
2809 - 2819
publisher
AlphaMed Press
external identifiers
  • wos:000250642200014
  • scopus:36249002298
ISSN
1549-4918
DOI
10.1634/stemcells.2006-0602
language
English
LU publication?
yes
id
8209718e-5ac1-4a8b-9dc5-89e47a619f35 (old id 651773)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17673527&dopt=Abstract
date added to LUP
2007-12-13 15:38:32
date last changed
2017-03-23 09:03:33
@article{8209718e-5ac1-4a8b-9dc5-89e47a619f35,
  abstract     = {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.},
  author       = {Moody, Jennifer and Singbrant, Sofie and Karlsson, Göran and Blank Savukinas, Ulrika and Aspling, Marie and Flygare, Johan and Bryder, David and Karlsson, Stefan},
  issn         = {1549-4918},
  keyword      = {erythropoiesis,RNA interference,hematopoiesis,stem cells},
  language     = {eng},
  number       = {11},
  pages        = {2809--2819},
  publisher    = {AlphaMed Press},
  series       = {Stem Cells},
  title        = {Endoglin is not critical for hematopoietic stem cell engraftment and reconstitution but regulates adult erythroid development},
  url          = {http://dx.doi.org/10.1634/stemcells.2006-0602},
  volume       = {25},
  year         = {2007},
}