Abstract
Jagged1-mediated Notch signaling has been suggested to be critically involved in hematopoietic stem cell (HSC) self-renewal. Unexpectedly, we report here that inducible Cre-loxP-mediated inactivation of the Jagged1 gene in bone marrow progenitors and/or bone marrow (BM) stromal cells does not impair HSC self-renewal or differentiation in all blood lineages. Mice with simultaneous inactivation of Jagged1 and Notch1 in the BM compartment survived normally following a 5FU-based in vivo challenge. In addition, Notch1-deficient HSCs were able to reconstitute mice with inactivated Jagged1 in the BM stroma even under competitive conditions. In contrast to earlier reports, these data exclude an essential role for Jagged1-mediated Notch signaling during hematopoiesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antimetabolites / administration & dosage
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Antimetabolites / toxicity
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Bone Marrow / physiology
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Calcium-Binding Proteins / deficiency
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Calcium-Binding Proteins / metabolism*
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Cell Proliferation*
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Fluorouracil / administration & dosage
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Fluorouracil / toxicity
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Hematopoiesis / drug effects
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Hematopoiesis / physiology
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / physiology*
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Integrases / genetics
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Intercellular Signaling Peptides and Proteins
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Jagged-1 Protein
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Membrane Proteins / deficiency
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Membrane Proteins / metabolism*
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Mice
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Mice, Transgenic
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Receptors, Notch / deficiency
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Receptors, Notch / metabolism*
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Serrate-Jagged Proteins
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Stromal Cells / cytology
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Stromal Cells / physiology
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Viral Proteins / genetics
Substances
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Antimetabolites
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Calcium-Binding Proteins
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Intercellular Signaling Peptides and Proteins
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Jag1 protein, mouse
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Jagged-1 Protein
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Membrane Proteins
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Receptors, Notch
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Serrate-Jagged Proteins
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Viral Proteins
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Cre recombinase
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Integrases
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Fluorouracil