Self-renewal of multipotent long-term repopulating hematopoietic stem cells is negatively regulated by Fas and tumor necrosis factor receptor activation

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Bibtex

@article{ae975bcfdc6843239708cd5fb06b507f,
title = "Self-renewal of multipotent long-term repopulating hematopoietic stem cells is negatively regulated by Fas and tumor necrosis factor receptor activation",
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.",
keywords = "hematopoietic stem cells, bone marrow transplantation, tumor necrosis factor, Fas, Fas ligand",
author = "David Bryder and Veslem{\o}y Ramsfjell and Ingunn Dybedal and Kim Theilgaard-Monch and Carl-Magnus H{\"o}gerkorp and J{\"o}rgen Adolfsson and Borge, {Ole Johan} and Jacobsen, {Sten Eirik W}",
year = "2001",
doi = "10.1084/jem.194.7.941",
language = "English",
volume = "194",
pages = "941--952",
journal = "Journal of Experimental Medicine",
issn = "1540-9538",
publisher = "Rockefeller University Press",
number = "7",

}