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Sökning: onr:"swepub:oai:lup.lub.lu.se:c3e8947b-bac6-4f28-ba35-913d11ddf620" > Tumor necrosis fact...

Tumor necrosis factor (TNF)-mediated activation of the p55 TNF receptor negatively regulates maintenance of cycling reconstituting human hematopoietic stem cells

Dybedal, Ingunn (författare)
Bryder, David (författare)
Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups
Fossum, Anna (författare)
Lund University,Lunds universitet,Stamcellscentrum (SCC),Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Department of Laboratory Medicine,Faculty of Medicine
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Rusten, Leiv S. (författare)
Jacobsen, Sten Eirik W (författare)
Lund University,Lunds universitet,Stamcellscentrum (SCC),Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Department of Laboratory Medicine,Faculty of Medicine
visa färre...
 (creator_code:org_t)
American Society of Hematology, 2001
2001
Engelska.
Ingår i: Blood. - : American Society of Hematology. - 1528-0020. ; 98:6, s. 1782-1791
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Hematopoietic stem cell (HSC) fate decisions between self-renewal and commitment toward differentiation are tightly regulated in vivo. Recent developments in HSC culture and improvements of human HSC assays have facilitated studies of these processes in vitro. Through such studies stimulatory cytokines critically involved in HSC maintenance in vivo have been demonstrated to also promote HSC self-renewing divisions in vitro. Evidence for negative regulators of HSC self-renewal is, however, lacking. Tumor necrosis factor (TNF), if overexpressed, has been implicated to mediate bone marrow suppression. However, whether and how TNF might affect the function of HSC with a combined myeloid and lymphoid reconstitution potential has not been investigated. In the present studies in vitro conditions recently demonstrated to promote HSC self-renewing divisions in vitro were used to study the effect of TNF on human HSCs capable of reconstituting myelopoiesis and lymphopoiesis in nonobese diabetic-severe combined immunodeficient (NOD-SCID) mice. Although all cord blood and adult bone marrow CD34(+)CD38(-) cells were capable of undergoing cell divisions in the presence of TNF, cycling HSCs exposed to TNF in vitro and in vivo were severely compromised in their ability to reconstitute NOD-SCID mice and long-term cultures. The negative effect of TNF was not dependent on the Fas pathway, and a similar effect could be observed using a mutant TNF exclusively targeting the p55 TNF receptor. TNF did not appear to enhance apoptosis or affect cell-cycle distribution of cultured progenitors, but rather promoted myeloid differentiation. Thus, TNF might regulate HSC fate by promoting their differentiation rather than self-renewal.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

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Av författaren/redakt...
Dybedal, Ingunn
Bryder, David
Fossum, Anna
Rusten, Leiv S.
Jacobsen, Sten E ...
Om ämnet
MEDICIN OCH HÄLSOVETENSKAP
MEDICIN OCH HÄLS ...
och Klinisk medicin
och Hematologi
MEDICIN OCH HÄLSOVETENSKAP
MEDICIN OCH HÄLS ...
och Klinisk medicin
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Blood
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Lunds universitet

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