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While 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 kappa (Rbpj), which canonical signaling through 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, following 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.

Original publication

DOI

10.1182/blood-2017-06-788505

Type

Journal article

Journal

Blood

Publication Date

16/01/2018

Addresses

Haematopoietic Stem Cell Biology Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.