Self-renewal of multipotent long-term repopulating hematopoietic stem cells is negatively regulated by Fas and tumor necrosis factor receptor activation
(2001) In Journal of Experimental Medicine 194(7). p.941-952- Abstract
- Multipotent self-renewing hematopoietic stem cells (HSCs) are responsible for reconstitution of all blood cell lineages. Whereas growth stimulatory cytokines have been demonstrated to promote HSC self-renewal, the potential role of negative regulators remains elusive. Receptors for tumor necrosis factor (TNF) and Fas ligand have been implicated as regulators of steady-state hematopoiesis, and if overexpressed mediate bone marrow failure. However, it has been proposed that hematopoietic progenitors rather than stem cells might be targeted by Fas activation. Here, murine Lin(-)Sca1(+)c-kit(+) stem cells revealed little or no constitutive expression of Fas and failed to respond to an agonistic anti-Fas antibody. However, if induced to undergo... (More)
- Multipotent self-renewing hematopoietic stem cells (HSCs) are responsible for reconstitution of all blood cell lineages. Whereas growth stimulatory cytokines have been demonstrated to promote HSC self-renewal, the potential role of negative regulators remains elusive. Receptors for tumor necrosis factor (TNF) and Fas ligand have been implicated as regulators of steady-state hematopoiesis, and if overexpressed mediate bone marrow failure. However, it has been proposed that hematopoietic progenitors rather than stem cells might be targeted by Fas activation. Here, murine Lin(-)Sca1(+)c-kit(+) stem cells revealed little or no constitutive expression of Fas and failed to respond to an agonistic anti-Fas antibody. However, if induced to undergo self-renewal in the presence of TNF-alpha, the entire short and long-term repopulating HSC pool acquired Fas expression at high levels and concomitant activation of Fas suppressed in vitro growth of Lin(-)Sca1(+)c-kit(+) cells cultured at the single cell level. Moreover, Lin(-)Sca1(+)c-kit(+) stem cells undergoing self-renewal divisions in vitro were severely and irreversibly compromised in their short- and long-term multilineage reconstituting ability if activated by TNF-alpha or through Fas, providing the first evidence for negative regulators of HSC self-renewal. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1121566
- author
- Bryder, David LU ; Ramsfjell, Veslemøy ; Dybedal, Ingunn ; Theilgaard-Monch, Kim ; Högerkorp, Carl-Magnus LU ; Adolfsson, Jörgen LU ; Borge, Ole Johan and Jacobsen, Sten Eirik W LU
- organization
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- hematopoietic stem cells, bone marrow transplantation, tumor necrosis factor, Fas, Fas ligand
- in
- Journal of Experimental Medicine
- volume
- 194
- issue
- 7
- pages
- 941 - 952
- publisher
- Rockefeller University Press
- external identifiers
-
- pmid:11581316
- scopus:0035477090
- ISSN
- 1540-9538
- DOI
- 10.1084/jem.194.7.941
- language
- English
- LU publication?
- yes
- id
- ae975bcf-dc68-4323-9708-cd5fb06b507f (old id 1121566)
- date added to LUP
- 2016-04-01 17:08:53
- date last changed
- 2022-07-31 21:35:52
@article{ae975bcf-dc68-4323-9708-cd5fb06b507f,
abstract = {{Multipotent self-renewing hematopoietic stem cells (HSCs) are responsible for reconstitution of all blood cell lineages. Whereas growth stimulatory cytokines have been demonstrated to promote HSC self-renewal, the potential role of negative regulators remains elusive. Receptors for tumor necrosis factor (TNF) and Fas ligand have been implicated as regulators of steady-state hematopoiesis, and if overexpressed mediate bone marrow failure. However, it has been proposed that hematopoietic progenitors rather than stem cells might be targeted by Fas activation. Here, murine Lin(-)Sca1(+)c-kit(+) stem cells revealed little or no constitutive expression of Fas and failed to respond to an agonistic anti-Fas antibody. However, if induced to undergo self-renewal in the presence of TNF-alpha, the entire short and long-term repopulating HSC pool acquired Fas expression at high levels and concomitant activation of Fas suppressed in vitro growth of Lin(-)Sca1(+)c-kit(+) cells cultured at the single cell level. Moreover, Lin(-)Sca1(+)c-kit(+) stem cells undergoing self-renewal divisions in vitro were severely and irreversibly compromised in their short- and long-term multilineage reconstituting ability if activated by TNF-alpha or through Fas, providing the first evidence for negative regulators of HSC self-renewal.}},
author = {{Bryder, David and Ramsfjell, Veslemøy and Dybedal, Ingunn and Theilgaard-Monch, Kim and Högerkorp, Carl-Magnus and Adolfsson, Jörgen and Borge, Ole Johan and Jacobsen, Sten Eirik W}},
issn = {{1540-9538}},
keywords = {{hematopoietic stem cells; bone marrow transplantation; tumor necrosis factor; Fas; Fas ligand}},
language = {{eng}},
number = {{7}},
pages = {{941--952}},
publisher = {{Rockefeller University Press}},
series = {{Journal of Experimental Medicine}},
title = {{Self-renewal of multipotent long-term repopulating hematopoietic stem cells is negatively regulated by Fas and tumor necrosis factor receptor activation}},
url = {{http://dx.doi.org/10.1084/jem.194.7.941}},
doi = {{10.1084/jem.194.7.941}},
volume = {{194}},
year = {{2001}},
}