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Upregulation of Flt3 expression within the bone marrow Lin(-)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity

Adolfsson, Jörgen LU ; Borge, O J; Bryder, David LU ; Theilgaard-Monch, K; Åstrand-Grundström, Ingbritt LU ; Sitnicka Quinn, Ewa LU ; Sasaki, Yutaka LU and Jacobsen, Sten Eirik W LU (2001) In Immunity 15(4). p.659-669
Abstract
Flt3 has emerged as a potential regulator of hematopoietic stem cells (HSC). Sixty percent of cells in the mouse marrow Lin(-)Sca1(+)c-kit(+) HSC pool expressed flt3. Although single cell cloning showed comparable high proliferative, myeloid, B, and T cell potentials of Lin(-)Sca1(+)c-kit(+)flt3(+) and Lin(-)Sca1(+)c-kit(+)flt3(-) cells, only Lin(-)Sca1(+)c-kit(+)flt3(-) cells supported sustained multilineage reconstitution. In striking contrast, Lin(-)Sca1(+)c-kit(+)flt3(+) cells rapidly and efficiently reconstituted B and T lymphopoiesis, whereas myeloid reconstitution was exclusively short term. Unlike c-kit, activation of flt3 failed to support survival of HSC, whereas only flt3 mediated survival of Lin(-)Sca1(+)c-kit(+)flt3(+)... (More)
Flt3 has emerged as a potential regulator of hematopoietic stem cells (HSC). Sixty percent of cells in the mouse marrow Lin(-)Sca1(+)c-kit(+) HSC pool expressed flt3. Although single cell cloning showed comparable high proliferative, myeloid, B, and T cell potentials of Lin(-)Sca1(+)c-kit(+)flt3(+) and Lin(-)Sca1(+)c-kit(+)flt3(-) cells, only Lin(-)Sca1(+)c-kit(+)flt3(-) cells supported sustained multilineage reconstitution. In striking contrast, Lin(-)Sca1(+)c-kit(+)flt3(+) cells rapidly and efficiently reconstituted B and T lymphopoiesis, whereas myeloid reconstitution was exclusively short term. Unlike c-kit, activation of flt3 failed to support survival of HSC, whereas only flt3 mediated survival of Lin(-)Sca1(+)c-kit(+)flt3(+) reconstituting cells. Phenotypic and functional analysis support that Lin(-)Sca1(+)c-kit(+)flt3(+) cells are progenitors for the common lymphoid progenitor. Thus, upregulation of flt3 expression on Lin(-)Sca1(+)c-kit(+) HSC cells is accompanied by loss of self-renewal capacity but sustained lymphoid-restricted reconstitution potential. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Immunity
volume
15
issue
4
pages
659 - 669
publisher
Cell Press
external identifiers
  • pmid:11672547
  • scopus:0034749999
ISSN
1074-7613
DOI
10.1016/S1074-7613(01)00220-5
language
English
LU publication?
yes
id
7bad8fbe-5572-4ef9-84d2-748f5600af5a (old id 1119997)
date added to LUP
2008-06-23 13:14:11
date last changed
2018-06-24 03:42:49
@article{7bad8fbe-5572-4ef9-84d2-748f5600af5a,
  abstract     = {Flt3 has emerged as a potential regulator of hematopoietic stem cells (HSC). Sixty percent of cells in the mouse marrow Lin(-)Sca1(+)c-kit(+) HSC pool expressed flt3. Although single cell cloning showed comparable high proliferative, myeloid, B, and T cell potentials of Lin(-)Sca1(+)c-kit(+)flt3(+) and Lin(-)Sca1(+)c-kit(+)flt3(-) cells, only Lin(-)Sca1(+)c-kit(+)flt3(-) cells supported sustained multilineage reconstitution. In striking contrast, Lin(-)Sca1(+)c-kit(+)flt3(+) cells rapidly and efficiently reconstituted B and T lymphopoiesis, whereas myeloid reconstitution was exclusively short term. Unlike c-kit, activation of flt3 failed to support survival of HSC, whereas only flt3 mediated survival of Lin(-)Sca1(+)c-kit(+)flt3(+) reconstituting cells. Phenotypic and functional analysis support that Lin(-)Sca1(+)c-kit(+)flt3(+) cells are progenitors for the common lymphoid progenitor. Thus, upregulation of flt3 expression on Lin(-)Sca1(+)c-kit(+) HSC cells is accompanied by loss of self-renewal capacity but sustained lymphoid-restricted reconstitution potential.},
  author       = {Adolfsson, Jörgen and Borge, O J and Bryder, David and Theilgaard-Monch, K and Åstrand-Grundström, Ingbritt and Sitnicka Quinn, Ewa and Sasaki, Yutaka and Jacobsen, Sten Eirik W},
  issn         = {1074-7613},
  language     = {eng},
  number       = {4},
  pages        = {659--669},
  publisher    = {Cell Press},
  series       = {Immunity},
  title        = {Upregulation of Flt3 expression within the bone marrow Lin(-)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity},
  url          = {http://dx.doi.org/10.1016/S1074-7613(01)00220-5},
  volume       = {15},
  year         = {2001},
}