Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling
Hematopoietic stem cells give rise to progeny that either self-renew in an undifferentiated state or lose self-renewal capabilities and commit to lymphoid or myeloid lineages. Here we evaluated whether hematopoietic stem cell self-renewal is affected by the Notch pathway. Notch signaling controls ce...
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Veröffentlicht in: | Nature medicine 2000-11, Vol.6 (11), p.1278-1281 |
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Sprache: | eng |
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Zusammenfassung: | Hematopoietic stem cells give rise to progeny that either self-renew in an undifferentiated state or lose self-renewal capabilities and commit to lymphoid or myeloid lineages. Here we evaluated whether hematopoietic stem cell self-renewal is affected by the Notch pathway. Notch signaling controls cell fate choices in both invertebrates and vertebrates
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,
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by inhibiting certain differentiation pathways, thereby permitting cells to either differentiate along an alternative pathway or to self-renew
1
. Notch receptors are present in hematopoietic precursors and Notch signaling enhances the
in vitro
generation of human and mouse hematopoietic precursors
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, determines T- or B-cell lineage specification from a common lymphoid precursor
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and promotes expansion of CD8
+
cells
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. Here, we demonstrate that constitutive Notch1 signaling in hematopoietic cells established immortalized, cytokine-dependent cell lines that generated progeny with either lymphoid or myeloid characteristics both
in vitro
and
in vivo
. These data support a role for Notch signaling in regulating hematopoietic stem cell self-renewal. Furthermore, the establishment of clonal, pluripotent cell lines provides the opportunity to assess mechanisms regulating stem cell commitment and demonstrates a general method for immortalizing stem cell populations for further analysis. |
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ISSN: | 1078-8956 1546-170X |
DOI: | 10.1038/81390 |