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Interleukin-7-induc...
Interleukin-7-induced Stat-5 Acts in Synergy with Flt-3 Signaling to Stimulate Expansion of Hematopoietic Progenitor Cells
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- Åhsberg, Josefine (author)
- Linköpings universitet,Experimentell hematologi,Hälsouniversitetet
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- Tsapogas, Panagiotis (author)
- Linköpings universitet,Experimentell hematologi,Hälsouniversitetet
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- Qian, Hong (author)
- Linköpings universitet,Experimentell hematologi,Hälsouniversitetet
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- Zetterblad, Jenny (author)
- Linköpings universitet,Experimentell hematologi,Hälsouniversitetet
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- Zandi, Sasan (author)
- Linköpings universitet,Experimentell hematologi,Hälsouniversitetet
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- Mansson, Robert (author)
- Linköpings universitet,Experimentell hematologi,Hälsouniversitetet
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- Jönsson, Jan-Ingvar (author)
- Linköpings universitet,Experimentell hematologi,Hälsouniversitetet
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- Sigvardsson, Mikael (author)
- Linköpings universitet,Experimentell hematologi,Hälsouniversitetet
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(creator_code:org_t)
- The American Society for Biochemistry and Molecular Biology, 2010
- 2010
- English.
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In: JOURNAL OF BIOLOGICAL CHEMISTRY. - : The American Society for Biochemistry and Molecular Biology. - 0021-9258. ; 285:47, s. 36275-36284
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- The development of lymphoid cells from bone marrow progenitors is dictated by interplay between internal cues such as transcription factors and external signals like the cytokines Flt-3 ligand and Il-7. These proteins are both of large importance for normal lymphoid development; however, it is unclear if they act in direct synergy to expand a transient Il-7R(+)Flt-3(+) population or if the collaboration is created through sequential activities. We report here that Flt-3L and Il-7 synergistically stimulated the expansion of primary Il-7R(+)Flt-3(+) progenitor cells and a hematopoietic progenitor cell line ectopically expressing the receptors. The stimulation resulted in a reduced expression of pro-apoptotic genes and also mediated survival of primary progenitor cells in vitro. However, functional analysis of single cells suggested that the anti-apoptotic effect was additive indicating that the synergy observed mainly depends on stimulation of proliferation. Analysis of downstream signaling events suggested that although Il-7 induced Stat-5 phosphorylation, Flt-3L caused activation of the ERK and AKT signaling pathways. Flt-3L could also drive proliferation in synergy with ectopically expressed constitutively active Stat-5. This synergy could be inhibited with either receptor tyrosine kinase or MAPK inhibitors suggesting that Flt-3L and Il-7 act in synergy by activation of independent signaling pathways to expand early hematopoietic progenitors.
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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