Canonical Notch signaling is dispensable for adult steady-state and stress myelo-erythropoiesis.
Sara DuartePetter S WollNatalija Buza-VidasDesmond Wai Loon ChinHanane BoukarabilaTiago C LuísLaura StensonTiphaine Bouriez-JonesHelen FerryAdam J MeadDeborah AtkinsonShaobo JinSally-Ann ClarkBishan WuEmmanouela RepapiNicki GrayStephen TaylorAnders P MutveiYat Long TsoiClaus NerlovUrban LendahlSten Eirik W JacobsenPublished in: Blood (2018)
Although an essential role for canonical Notch signaling in generation of hematopoietic stem cells in the embryo and in thymic T-cell development is well established, its role in adult bone marrow (BM) myelopoiesis remains unclear. Some studies, analyzing myeloid progenitors in adult mice with inhibited Notch signaling, implicated distinct roles of canonical Notch signaling in regulation of progenitors for the megakaryocyte, erythroid, and granulocyte-macrophage cell lineages. However, these studies might also have targeted other pathways. Therefore, we specifically deleted, in adult BM, the transcription factor recombination signal-binding protein J κ (Rbpj), through which canonical signaling from all Notch receptors converges. Notably, detailed progenitor staging established that canonical Notch signaling is fully dispensable for all investigated stages of megakaryocyte, erythroid, and myeloid progenitors in steady state unperturbed hematopoiesis, after competitive BM transplantation, and in stress-induced erythropoiesis. Moreover, expression of key regulators of these hematopoietic lineages and Notch target genes were unaffected by Rbpj deficiency in BM progenitor cells.
Keyphrases
- bone marrow
- stress induced
- stem cells
- transcription factor
- binding protein
- mesenchymal stem cells
- cell therapy
- cell proliferation
- acute myeloid leukemia
- childhood cancer
- poor prognosis
- adipose tissue
- lymph node
- pregnant women
- immune response
- mass spectrometry
- type diabetes
- drug delivery
- metabolic syndrome
- high resolution
- pet ct
- young adults
- dna repair
- smoking cessation