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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/651773
- author
- 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
- organization
- publishing date
- 2007
- 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
- Oxford University 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
- 2016-04-01 15:40:27
- date last changed
- 2023-01-04 18:31:06
@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}},
keywords = {{erythropoiesis; RNA interference; hematopoiesis; stem cells}},
language = {{eng}},
number = {{11}},
pages = {{2809--2819}},
publisher = {{Oxford University 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}},
doi = {{10.1634/stemcells.2006-0602}},
volume = {{25}},
year = {{2007}},
}