Jagged1-dependent Notch signaling is dispensable for hematopoietic stem cell self-renewal and differentiation.
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.
Mancini
Stéphane J C
SJ
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland.
Mantei
Ned
N
Dumortier
Alexis
A
Suter
Ueli
U
MacDonald
H Robson
HR
Radtke
Freddy
F
D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000633:toxicity; D001853:Bone Marrow / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation; D005472:Fluorouracil / Q000008:administration & dosage / Q000633:toxicity; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D019426:Integrases / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D051880:Receptors, Notch / Q000172:deficiency / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics
D000963:Antimetabolites; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases; D005472:Fluorouracil