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FLT3 receptor and ligand are dispensable for maintenance and posttransplantation expansion of mouse hematopoietic stem cells

Buza-Vidas, Natalija LU ; Cheng, Min LU ; Duarte, Sara LU ; NozadCharoudeh, Hojjatollah LU ; Jacobsen, Sten Eirik W LU and Sitnicka Quinn, Ewa LU (2009) In Blood 113(15). p.3453-3460
Abstract
Originally cloned from hematopoietic stem cell (HSC) populations and its ligand being extensively used to promote ex vivo HSC expansion, the FMS-like tyrosine kinase 3 (FLT3; also called FLK2) receptor and its ligand (FL) were expected to emerge as an important physiologic regulator of HSC maintenance and expansion. However, the role of FLT3 receptor and ligand in HSC regulation remains unclear and disputed. Herein, using Fl-deficient mice, we establish for the first time that HSC expansion in fetal liver and after transplantation is FL independent. Because previous findings in Flk2(-/-) mice were compatible with an important role of FLT3 receptor in HSC regulation and because alternative ligands might potentially interact directly or... (More)
Originally cloned from hematopoietic stem cell (HSC) populations and its ligand being extensively used to promote ex vivo HSC expansion, the FMS-like tyrosine kinase 3 (FLT3; also called FLK2) receptor and its ligand (FL) were expected to emerge as an important physiologic regulator of HSC maintenance and expansion. However, the role of FLT3 receptor and ligand in HSC regulation remains unclear and disputed. Herein, using Fl-deficient mice, we establish for the first time that HSC expansion in fetal liver and after transplantation is FL independent. Because previous findings in Flk2(-/-) mice were compatible with an important role of FLT3 receptor in HSC regulation and because alternative ligands might potentially interact directly or indirectly with FLT3 receptor, we here also characterized HSCs in Flk2(-/-) mice. Advanced phenotypic as well as functional evaluation of Flk2(-/-) HSCs showed that the FLT3 receptor is dispensable for HSC steady-state maintenance and expansion after transplantation. Taken together, these studies show that the FLT3 receptor and ligand are not critical regulators of mouse HSCs, neither in steady state nor during fetal or posttransplantation expansion. (Blood. 2009; 113: 3453-3460) (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
113
issue
15
pages
3453 - 3460
publisher
American Society of Hematology
external identifiers
  • wos:000265052300010
  • pmid:19188666
  • scopus:65349147139
ISSN
1528-0020
DOI
10.1182/blood-2008-08-174060
language
English
LU publication?
yes
id
8db14e1e-bb30-4c1a-9cd7-7b108d34ed04 (old id 1400750)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19188666?dopt=Abstract
date added to LUP
2009-06-15 13:05:23
date last changed
2017-09-24 03:43:40
@article{8db14e1e-bb30-4c1a-9cd7-7b108d34ed04,
  abstract     = {Originally cloned from hematopoietic stem cell (HSC) populations and its ligand being extensively used to promote ex vivo HSC expansion, the FMS-like tyrosine kinase 3 (FLT3; also called FLK2) receptor and its ligand (FL) were expected to emerge as an important physiologic regulator of HSC maintenance and expansion. However, the role of FLT3 receptor and ligand in HSC regulation remains unclear and disputed. Herein, using Fl-deficient mice, we establish for the first time that HSC expansion in fetal liver and after transplantation is FL independent. Because previous findings in Flk2(-/-) mice were compatible with an important role of FLT3 receptor in HSC regulation and because alternative ligands might potentially interact directly or indirectly with FLT3 receptor, we here also characterized HSCs in Flk2(-/-) mice. Advanced phenotypic as well as functional evaluation of Flk2(-/-) HSCs showed that the FLT3 receptor is dispensable for HSC steady-state maintenance and expansion after transplantation. Taken together, these studies show that the FLT3 receptor and ligand are not critical regulators of mouse HSCs, neither in steady state nor during fetal or posttransplantation expansion. (Blood. 2009; 113: 3453-3460)},
  author       = {Buza-Vidas, Natalija and Cheng, Min and Duarte, Sara and NozadCharoudeh, Hojjatollah and Jacobsen, Sten Eirik W and Sitnicka Quinn, Ewa},
  issn         = {1528-0020},
  language     = {eng},
  number       = {15},
  pages        = {3453--3460},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {FLT3 receptor and ligand are dispensable for maintenance and posttransplantation expansion of mouse hematopoietic stem cells},
  url          = {http://dx.doi.org/10.1182/blood-2008-08-174060},
  volume       = {113},
  year         = {2009},
}