Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 98, Issue 4, Pages 1757-1762Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.98.4.1757
Keywords
IL-6; serum-free culture
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Funding
- NHLBI NIH HHS [P01-HL55435, P01 HL055435] Funding Source: Medline
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Previous studies have demonstrated hematopoietic stem cell amplification in vitro after the activation of three cell-surface receptors: flt3/fik2, c-kit, and gp130, We now show flt3-ligand and Steel factor alone will stimulate >85% of c-kit(+)Sca-1(+)lin(-) adult mouse bone marrow cells to proliferate in single-cell serum-free cultures, but concomitant retention of their stem cell activity requires additional exposure to a ligand that will activate gp130, Moreover, this response is restricted to a narrow range of gp130-activating ligand concentrations, above and below which hematopoietic stem cell activity is lost. These findings indicate a unique contribution of gp130 signaling to the maintenance of hematopoietic stem cell function when these cells are stimulated to divide with additional differential effects dictated by the intensity of gp130 activation.
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